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  • 1
    Publication Date: 2010-10-12
    Description: Jasmonates are a family of plant hormones that regulate plant growth, development and responses to stress. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JAZ proteins. Despite its importance, the mechanism of jasmonate perception remains unclear. Here we present structural and pharmacological data to show that the true Arabidopsis jasmonate receptor is a complex of both COI1 and JAZ. COI1 contains an open pocket that recognizes the bioactive hormone (3R,7S)-jasmonoyl-l-isoleucine (JA-Ile) with high specificity. High-affinity hormone binding requires a bipartite JAZ degron sequence consisting of a conserved alpha-helix for COI1 docking and a loop region to trap the hormone in its binding pocket. In addition, we identify a third critical component of the jasmonate co-receptor complex, inositol pentakisphosphate, which interacts with both COI1 and JAZ adjacent to the ligand. Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988090/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheard, Laura B -- Tan, Xu -- Mao, Haibin -- Withers, John -- Ben-Nissan, Gili -- Hinds, Thomas R -- Kobayashi, Yuichi -- Hsu, Fong-Fu -- Sharon, Michal -- Browse, John -- He, Sheng Yang -- Rizo, Josep -- Howe, Gregg A -- Zheng, Ning -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-10/DK/NIDDK NIH HHS/ -- R01 AI068718/AI/NIAID NIH HHS/ -- R01 AI068718-04/AI/NIAID NIH HHS/ -- R01 CA107134/CA/NCI NIH HHS/ -- R01 CA107134-07/CA/NCI NIH HHS/ -- R01 GM057795/GM/NIGMS NIH HHS/ -- R01 GM057795-12/GM/NIGMS NIH HHS/ -- R01AI068718/AI/NIAID NIH HHS/ -- R01GM57795/GM/NIGMS NIH HHS/ -- T32 GM07270/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Nov 18;468(7322):400-5. doi: 10.1038/nature09430. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927106" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acids/chemistry/metabolism ; Arabidopsis/chemistry/metabolism ; Arabidopsis Proteins/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Cyclopentanes/chemistry/*metabolism ; F-Box Proteins/chemistry/metabolism ; Indenes/chemistry/metabolism ; Inositol Phosphates/*metabolism ; Isoleucine/analogs & derivatives/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Oxylipins/chemistry/*metabolism ; Peptide Fragments/chemistry/metabolism ; Plant Growth Regulators/chemistry/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry/*metabolism ; Signal Transduction
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  • 2
    Publication Date: 2009-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheard, Laura B -- Zheng, Ning -- England -- Nature. 2009 Dec 3;462(7273):575-6. doi: 10.1038/462575a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956245" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/metabolism/*physiology ; Ligands ; *Plant Physiological Phenomena ; Plant Proteins/chemistry/metabolism ; Protoplasts/physiology ; Signal Transduction/*physiology
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  • 3
    Publication Date: 2012-06-09
    Description: In excitable cells, voltage-gated sodium (Na(V)) channels activate to initiate action potentials and then undergo fast and slow inactivation processes that terminate their ionic conductance. Inactivation is a hallmark of Na(V) channel function and is critical for control of membrane excitability, but the structural basis for this process has remained elusive. Here we report crystallographic snapshots of the wild-type Na(V)Ab channel from Arcobacter butzleri captured in two potentially inactivated states at 3.2 A resolution. Compared to previous structures of Na(V)Ab channels with cysteine mutations in the pore-lining S6 helices (ref. 4), the S6 helices and the intracellular activation gate have undergone significant rearrangements: one pair of S6 helices has collapsed towards the central pore axis and the other S6 pair has moved outward to produce a striking dimer-of-dimers configuration. An increase in global structural asymmetry is observed throughout our wild-type Na(V)Ab models, reshaping the ion selectivity filter at the extracellular end of the pore, the central cavity and its residues that are analogous to the mammalian drug receptor site, and the lateral pore fenestrations. The voltage-sensing domains have also shifted around the perimeter of the pore module in wild-type Na(V)Ab, compared to the mutant channel, and local structural changes identify a conserved interaction network that connects distant molecular determinants involved in Na(V) channel gating and inactivation. These potential inactivated-state structures provide new insights into Na(V) channel gating and novel avenues to drug development and therapy for a range of debilitating Na(V) channelopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552482/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payandeh, Jian -- Gamal El-Din, Tamer M -- Scheuer, Todd -- Zheng, Ning -- Catterall, William A -- R01 HL112808/HL/NHLBI NIH HHS/ -- R01 NS015751/NS/NINDS NIH HHS/ -- R01 NS15751/NS/NINDS NIH HHS/ -- U01 NS058039/NS/NINDS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 May 20;486(7401):135-9. doi: 10.1038/nature11077.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678296" target="_blank"〉PubMed〈/a〉
    Keywords: Arcobacter/*chemistry ; Conserved Sequence ; Crystallization ; Crystallography, X-Ray ; *Ion Channel Gating ; Models, Molecular ; Protein Conformation ; Sodium Channels/*chemistry/metabolism ; Structure-Activity Relationship
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  • 4
    Publication Date: 2013-03-19
    Description: The cryptochrome (CRY) flavoproteins act as blue-light receptors in plants and insects, but perform light-independent functions at the core of the mammalian circadian clock. To drive clock oscillations, mammalian CRYs associate with the Period proteins (PERs) and together inhibit the transcription of their own genes. The SCF(FBXL3) ubiquitin ligase complex controls this negative feedback loop by promoting CRY ubiquitination and degradation. However, the molecular mechanisms of their interactions and the functional role of flavin adenine dinucleotide (FAD) binding in CRYs remain poorly understood. Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms. Distinct from other cryptochromes of known structures, mammalian CRY2 binds FAD dynamically with an open cofactor pocket. Notably, the F-box protein FBXL3 captures CRY2 by simultaneously occupying its FAD-binding pocket with a conserved carboxy-terminal tail and burying its PER-binding interface. This novel F-box-protein-substrate bipartite interaction is susceptible to disruption by both FAD and PERs, suggesting a new avenue for pharmacological targeting of the complex and a multifaceted regulatory mechanism of CRY ubiquitination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618506/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618506/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xing, Weiman -- Busino, Luca -- Hinds, Thomas R -- Marionni, Samuel T -- Saifee, Nabiha H -- Bush, Matthew F -- Pagano, Michele -- Zheng, Ning -- 5T32-HL007151/HL/NHLBI NIH HHS/ -- K99 CA166181/CA/NCI NIH HHS/ -- R01 GM057587/GM/NIGMS NIH HHS/ -- R01-CA107134/CA/NCI NIH HHS/ -- R01-GM057587/GM/NIGMS NIH HHS/ -- R21-CA161108/CA/NCI NIH HHS/ -- R37 CA076584/CA/NCI NIH HHS/ -- R37-CA-076584/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Apr 4;496(7443):64-8. doi: 10.1038/nature11964. Epub 2013 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23503662" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoproteins/chemistry/metabolism ; Binding Sites ; Cryptochromes/chemistry/*metabolism ; Crystallography, X-Ray ; Deoxyribodipyrimidine Photo-Lyase/chemistry ; Drosophila melanogaster/chemistry ; F-Box Proteins/chemistry/*metabolism ; Flavin-Adenine Dinucleotide/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Mice ; Models, Molecular ; Protein Structure, Tertiary ; S-Phase Kinase-Associated Proteins/chemistry/metabolism ; SKP Cullin F-Box Protein Ligases/chemistry/*metabolism ; Substrate Specificity
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  • 5
    Publication Date: 2013-12-18
    Description: Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the alpha/beta hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096652/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096652/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Feng -- Lin, Qibing -- Zhu, Lihong -- Ren, Yulong -- Zhou, Kunneng -- Shabek, Nitzan -- Wu, Fuqing -- Mao, Haibin -- Dong, Wei -- Gan, Lu -- Ma, Weiwei -- Gao, He -- Chen, Jun -- Yang, Chao -- Wang, Dan -- Tan, Junjie -- Zhang, Xin -- Guo, Xiuping -- Wang, Jiulin -- Jiang, Ling -- Liu, Xi -- Chen, Weiqi -- Chu, Jinfang -- Yan, Cunyu -- Ueno, Kotomi -- Ito, Shinsaku -- Asami, Tadao -- Cheng, Zhijun -- Wang, Jie -- Lei, Cailin -- Zhai, Huqu -- Wu, Chuanyin -- Wang, Haiyang -- Zheng, Ning -- Wan, Jianmin -- R01 CA107134/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Dec 19;504(7480):406-10. doi: 10.1038/nature12878. Epub 2013 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] National Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing 210095, China [2] National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China. ; National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China. ; National Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing 210095, China. ; 1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, Box 357280, University of Washington, Seattle, Washington 98195, USA. ; National Centre for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 1-2 Beichen West Road, Beijing 100101, China. ; Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24336215" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Lactones/*metabolism ; Molecular Sequence Data ; Mutation/genetics ; Oryza/genetics/*metabolism ; Phenotype ; Plant Growth Regulators/*metabolism ; Plant Proteins/genetics/*metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; *Proteolysis ; SKP Cullin F-Box Protein Ligases/*metabolism ; *Signal Transduction
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  • 6
    Publication Date: 2014-02-28
    Description: Nitrate is a primary nutrient for plant growth, but its levels in soil can fluctuate by several orders of magnitude. Previous studies have identified Arabidopsis NRT1.1 as a dual-affinity nitrate transporter that can take up nitrate over a wide range of concentrations. The mode of action of NRT1.1 is controlled by phosphorylation of a key residue, Thr 101; however, how this post-translational modification switches the transporter between two affinity states remains unclear. Here we report the crystal structure of unphosphorylated NRT1.1, which reveals an unexpected homodimer in the inward-facing conformation. In this low-affinity state, the Thr 101 phosphorylation site is embedded in a pocket immediately adjacent to the dimer interface, linking the phosphorylation status of the transporter to its oligomeric state. Using a cell-based fluorescence resonance energy transfer assay, we show that functional NRT1.1 dimerizes in the cell membrane and that the phosphomimetic mutation of Thr 101 converts the protein into a monophasic high-affinity transporter by structurally decoupling the dimer. Together with analyses of the substrate transport tunnel, our results establish a phosphorylation-controlled dimerization switch that allows NRT1.1 to uptake nitrate with two distinct affinity modes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968801/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968801/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Ji -- Bankston, John R -- Payandeh, Jian -- Hinds, Thomas R -- Zagotta, William N -- Zheng, Ning -- NS074545/NS/NINDS NIH HHS/ -- R01EY10329/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 6;507(7490):73-7. doi: 10.1038/nature13074. Epub 2014 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA. ; Department of Physiology and Biophysics, Box 357290, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA [2] Department of Structural Biology, Genentech Inc., South San Francisco, California 94080, USA. ; 1] Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, Box 357280, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572362" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anion Transport Proteins/*chemistry/genetics/metabolism ; Arabidopsis/*chemistry/genetics ; Binding Sites ; Biological Transport ; Cell Membrane/chemistry/metabolism ; Crystallography, X-Ray ; Fluorescence Resonance Energy Transfer ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Mutation/genetics ; Nitrates/chemistry/metabolism ; Phosphorylation ; Phosphothreonine/chemistry/metabolism ; Plant Proteins/*chemistry/genetics/metabolism ; *Protein Multimerization ; Protein Structure, Quaternary ; Protons ; Structure-Activity Relationship
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  • 7
    Publication Date: 2011-07-12
    Description: Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na(+) channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 A resolution. The arginine gating charges make multiple hydrophilic interactions within the voltage sensor, including unanticipated hydrogen bonds to the protein backbone. Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4-S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. The NavAb selectivity filter is short, approximately 4.6 A wide, and water filled, with four acidic side chains surrounding the narrowest part of the ion conduction pathway. This unique structure presents a high-field-strength anionic coordination site, which confers Na(+) selectivity through partial dehydration via direct interaction with glutamate side chains. Fenestrations in the sides of the pore module are unexpectedly penetrated by fatty acyl chains that extend into the central cavity, and these portals are large enough for the entry of small, hydrophobic pore-blocking drugs. This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266868/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266868/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payandeh, Jian -- Scheuer, Todd -- Zheng, Ning -- Catterall, William A -- R01 NS015751/NS/NINDS NIH HHS/ -- R01 NS015751-24/NS/NINDS NIH HHS/ -- R01 NS15751/NS/NINDS NIH HHS/ -- U01 NS058039/NS/NINDS NIH HHS/ -- U01 NS058039-03/NS/NINDS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jul 10;475(7356):353-8. doi: 10.1038/nature10238.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21743477" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arcobacter/*chemistry ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Calcium/metabolism ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; *Ion Channel Gating ; Ion Transport ; Models, Molecular ; Potassium/metabolism ; Potassium Channels/chemistry/metabolism ; Protein Conformation ; Sodium/metabolism ; Sodium Channel Blockers/chemistry/metabolism/pharmacology ; Sodium Channels/*chemistry/*metabolism ; Structure-Activity Relationship ; Substrate Specificity
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  • 8
    Publication Date: 2012-06-16
    Description: Salicylic acid (SA) is a plant immune signal produced after pathogen challenge to induce systemic acquired resistance. It is the only major plant hormone for which the receptor has not been firmly identified. Systemic acquired resistance in Arabidopsis requires the transcription cofactor nonexpresser of PR genes 1 (NPR1), the degradation of which acts as a molecular switch. Here we show that the NPR1 paralogues NPR3 and NPR4 are SA receptors that bind SA with different affinities. NPR3 and NPR4 function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the Arabidopsis npr3 npr4 double mutant accumulates higher levels of NPR1, and is insensitive to induction of systemic acquired resistance. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376392/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376392/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, Zheng Qing -- Yan, Shunping -- Saleh, Abdelaty -- Wang, Wei -- Ruble, James -- Oka, Nodoka -- Mohan, Rajinikanth -- Spoel, Steven H -- Tada, Yasuomi -- Zheng, Ning -- Dong, Xinnian -- CA107134/CA/NCI NIH HHS/ -- GM069594-05/GM/NIGMS NIH HHS/ -- R01 CA107134/CA/NCI NIH HHS/ -- R01 GM069594/GM/NIGMS NIH HHS/ -- T32 GM008268/GM/NIGMS NIH HHS/ -- T32GM008268-23/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 May 16;486(7402):228-32. doi: 10.1038/nature11162.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Department of Biology, PO Box 90338, Duke University, Durham, North Carolina 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22699612" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics/immunology/*metabolism ; Arabidopsis Proteins/genetics/metabolism ; Mutation ; Protein Binding ; Salicylic Acid/*metabolism ; *Signal Transduction ; Two-Hybrid System Techniques ; Ubiquitin-Protein Ligases/metabolism
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  • 9
    Publication Date: 2013-11-26
    Description: Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of Ca(2+) into cells despite a 70-fold higher extracellular concentration of Na(+). How CaV channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial NaV channel NaVAb. Our results reveal interactions of hydrated Ca(2+) with two high-affinity Ca(2+)-binding sites followed by a third lower-affinity site that would coordinate Ca(2+) as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca(2+) selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd(2+) and Mn(2+), with single occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone, which mediate exit into the central cavity. This pore architecture suggests a conduction pathway involving transitions between two main states with one or two hydrated Ca(2+) ions bound in the selectivity filter and supports a 'knock-off' mechanism of ion permeation through a stepwise-binding process. The multi-ion selectivity filter of our CaVAb model establishes a structural framework for understanding the mechanisms of ion selectivity and conductance by vertebrate CaV channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877713/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Lin -- Gamal El-Din, Tamer M -- Payandeh, Jian -- Martinez, Gilbert Q -- Heard, Teresa M -- Scheuer, Todd -- Zheng, Ning -- Catterall, William A -- R01 HL112808/HL/NHLBI NIH HHS/ -- R01 HL117896/HL/NHLBI NIH HHS/ -- R01 NS015751/NS/NINDS NIH HHS/ -- R01HL112808/HL/NHLBI NIH HHS/ -- R01NS015751/NS/NINDS NIH HHS/ -- T32 GM008268/GM/NIGMS NIH HHS/ -- T32GM008268/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 2;505(7481):56-61. doi: 10.1038/nature12775. Epub 2013 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA [3]. ; 1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2]. ; 1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2] Department of Structural Biology, Genentech Inc., South San Francisco, California 94080, USA. ; Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24270805" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics/*metabolism ; Binding Sites ; Biocatalysis ; Calcium/metabolism ; Calcium Channels/*chemistry/genetics/*metabolism ; Cations, Divalent/metabolism ; Crystallography, X-Ray ; Electric Conductivity ; *Ion Channel Gating ; Models, Biological ; Models, Molecular ; Structure-Activity Relationship ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2016-01-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Feng -- Lin, Qibing -- Zhu, Lihong -- Ren, Yulong -- Zhou, Kunneng -- Shabek, Nitzan -- Wu, Fuqing -- Mao, Haibin -- Dong, Wei -- Gan, Lu -- Ma, Weiwei -- Gao, He -- Chen, Jun -- Yang, Chao -- Wang, Dan -- Tan, Junjie -- Zhang, Xin -- Guo, Xiuping -- Wang, Jiulin -- Jiang, Ling -- Liu, Xi -- Chen, Weiqi -- Chu, Jinfang -- Yan, Cunyu -- Ueno, Kotomi -- Ito, Shinsaku -- Asami, Tadao -- Cheng, Zhijun -- Wang, Jie -- Lei, Cailin -- Zhai, Huqu -- Wu, Chuanyin -- Wang, Haiyang -- Zheng, Ning -- Wan, Jianmin -- England -- Nature. 2016 Apr 21;532(7599):402. doi: 10.1038/nature16537. Epub 2016 Jan 13.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26760207" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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