ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2010-08-21
    Description: Propionyl-coenzyme A carboxylase (PCC), a mitochondrial biotin-dependent enzyme, is essential for the catabolism of the amino acids Thr, Val, Ile and Met, cholesterol and fatty acids with an odd number of carbon atoms. Deficiencies in PCC activity in humans are linked to the disease propionic acidaemia, an autosomal recessive disorder that can be fatal in infants. The holoenzyme of PCC is an alpha(6)beta(6) dodecamer, with a molecular mass of 750 kDa. The alpha-subunit contains the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains, whereas the beta-subunit supplies the carboxyltransferase (CT) activity. Here we report the crystal structure at 3.2-A resolution of a bacterial PCC alpha(6)beta(6) holoenzyme as well as cryo-electron microscopy (cryo-EM) reconstruction at 15-A resolution demonstrating a similar structure for human PCC. The structure defines the overall architecture of PCC and reveals unexpectedly that the alpha-subunits are arranged as monomers in the holoenzyme, decorating a central beta(6) hexamer. A hitherto unrecognized domain in the alpha-subunit, formed by residues between the BC and BCCP domains, is crucial for interactions with the beta-subunit. We have named it the BT domain. The structure reveals for the first time the relative positions of the BC and CT active sites in the holoenzyme. They are separated by approximately 55 A, indicating that the entire BCCP domain must translocate during catalysis. The BCCP domain is located in the active site of the beta-subunit in the current structure, providing insight for its involvement in the CT reaction. The structural information establishes a molecular basis for understanding the large collection of disease-causing mutations in PCC and is relevant for the holoenzymes of other biotin-dependent carboxylases, including 3-methylcrotonyl-CoA carboxylase (MCC) and eukaryotic acetyl-CoA carboxylase (ACC).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925307/" 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/PMC2925307/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Christine S -- Sadre-Bazzaz, Kianoush -- Shen, Yang -- Deng, Binbin -- Zhou, Z Hong -- Tong, Liang -- AI069015/AI/NIAID NIH HHS/ -- DK067238/DK/NIDDK NIH HHS/ -- GM071940/GM/NIGMS NIH HHS/ -- GM08281/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI069015/AI/NIAID NIH HHS/ -- R01 AI069015-04/AI/NIAID NIH HHS/ -- R01 DK067238/DK/NIDDK NIH HHS/ -- R01 DK067238-07/DK/NIDDK NIH HHS/ -- R01 GM071940/GM/NIGMS NIH HHS/ -- R01 GM071940-05/GM/NIGMS NIH HHS/ -- T32 GM008281/GM/NIGMS NIH HHS/ -- T32 GM008281-23/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 19;466(7309):1001-5. doi: 10.1038/nature09302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, New York 10027, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725044" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyl-CoA Carboxylase/chemistry/metabolism/ultrastructure ; Biocatalysis ; Biotin/metabolism ; Carbon-Nitrogen Ligases/chemistry/metabolism/ultrastructure ; Carrier Proteins/chemistry/metabolism/ultrastructure ; Catalytic Domain ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; Fatty Acid Synthase, Type II ; Holoenzymes/*chemistry/genetics/metabolism/*ultrastructure ; Humans ; Methylmalonyl-CoA Decarboxylase/*chemistry/genetics/metabolism/*ultrastructure ; Models, Molecular ; Mutation/genetics ; Propionic Acidemia/enzymology/genetics ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Rhodobacteraceae/enzymology ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2015-10-28
    Description: Viruses in the Reoviridae, like the triple-shelled human rotavirus and the single-shelled insect cytoplasmic polyhedrosis virus (CPV), all package a genome of segmented double-stranded RNAs (dsRNAs) inside the viral capsid and carry out endogenous messenger RNA synthesis through a transcriptional enzyme complex (TEC). By direct electron-counting cryoelectron microscopy and asymmetric reconstruction, we have determined the organization of the dsRNA genome inside quiescent CPV (q-CPV) and the in situ atomic structures of TEC within CPV in both quiescent and transcribing (t-CPV) states. We show that the ten segmented dsRNAs in CPV are organized with ten TECs in a specific, non-symmetric manner, with each dsRNA segment attached directly to a TEC. The TEC consists of two extensively interacting subunits: an RNA-dependent RNA polymerase (RdRP) and an NTPase VP4. We find that the bracelet domain of RdRP undergoes marked conformational change when q-CPV is converted to t-CPV, leading to formation of the RNA template entry channel and access to the polymerase active site. An amino-terminal helix from each of two subunits of the capsid shell protein (CSP) interacts with VP4 and RdRP. These findings establish the link between sensing of environmental cues by the external proteins and activation of endogenous RNA transcription by the TEC inside the virus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Xing -- Ding, Ke -- Yu, Xuekui -- Chang, Winston -- Sun, Jingchen -- Zhou, Z Hong -- 1S10OD018111/OD/NIH HHS/ -- 1S10RR23057/RR/NCRR NIH HHS/ -- AI094386/AI/NIAID NIH HHS/ -- GM071940/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Nov 26;527(7579):531-4. doi: 10.1038/nature15767. Epub 2015 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Nanosystems Institute, University of California, Los Angeles, California 90095, USA. ; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA. ; Bioengineering, University of California, Los Angeles, California 90095, USA. ; Subtropical Sericulture and Mulberry Resources Protection and Safety Engineering Research Center, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26503045" target="_blank"〉PubMed〈/a〉
    Keywords: Capsid Proteins/chemistry/metabolism/ultrastructure ; Catalytic Domain ; Cryoelectron Microscopy ; *Genome, Viral/genetics ; Models, Molecular ; Multienzyme Complexes/chemistry/metabolism/*ultrastructure ; Nucleoside-Triphosphatase/metabolism/ultrastructure ; Protein Subunits/chemistry/metabolism ; RNA Replicase/chemistry/metabolism/*ultrastructure ; RNA, Double-Stranded/genetics/*ultrastructure ; RNA, Messenger/biosynthesis/genetics/ultrastructure ; RNA, Viral/biosynthesis/genetics/*ultrastructure ; Reoviridae/enzymology/genetics/*ultrastructure ; Templates, Genetic ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...