ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
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
    facet.materialart.
    Unknown
    Structure-based assembly of protein complexes in yeast (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-03-27
    Description: Images of entire cells are preceding atomic structures of the separate molecular machines that they contain. The resulting gap in knowledge can be partly bridged by protein-protein interactions, bioinformatics, and electron microscopy. Here we use interactions of known three-dimensional structure to model a large set of yeast complexes, which we also screen by electron microscopy. For 54 of 102 complexes, we obtain at least partial models of interacting subunits. For 29, including the exosome, the chaperonin containing TCP-1, a 3'-messenger RNA degradation complex, and RNA polymerase II, the process suggests atomic details not easily seen by homology, involving the combination of two or more known structures. We also consider interactions between complexes (cross-talk) and use these to construct a structure-based network of molecular machines in the cell.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aloy, Patrick -- Bottcher, Bettina -- Ceulemans, Hugo -- Leutwein, Christina -- Mellwig, Christian -- Fischer, Susanne -- Gavin, Anne-Claude -- Bork, Peer -- Superti-Furga, Giulio -- Serrano, Luis -- Russell, Robert B -- New York, N.Y. -- Science. 2004 Mar 26;303(5666):2026-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Programme, 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15044803" target="_blank"〉PubMed〈/a〉
    Keywords: Chaperonins/chemistry/metabolism ; Computational Biology ; Image Processing, Computer-Assisted ; Microscopy, Electron ; Models, Biological ; Models, Molecular ; Nuclear Proteins/chemistry/metabolism ; Protein Binding ; Protein Conformation ; *Protein Interaction Mapping ; Protein Structure, Tertiary ; RNA Polymerase II/chemistry/metabolism ; Ribonuclease P/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/*metabolism/ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Transcription Factors/chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-07-22
    Description: In the 1950s, the drug thalidomide, administered as a sedative to pregnant women, led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-associated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4(CRBN). Here we present crystal structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs. Using an unbiased screen, we identified the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4(CRBN). Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423819/" 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/PMC4423819/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Eric S -- Bohm, Kerstin -- Lydeard, John R -- Yang, Haidi -- Stadler, Michael B -- Cavadini, Simone -- Nagel, Jane -- Serluca, Fabrizio -- Acker, Vincent -- Lingaraju, Gondichatnahalli M -- Tichkule, Ritesh B -- Schebesta, Michael -- Forrester, William C -- Schirle, Markus -- Hassiepen, Ulrich -- Ottl, Johannes -- Hild, Marc -- Beckwith, Rohan E J -- Harper, J Wade -- Jenkins, Jeremy L -- Thoma, Nicolas H -- AG011085/AG/NIA NIH HHS/ -- R01 AG011085/AG/NIA NIH HHS/ -- England -- Nature. 2014 Aug 7;512(7512):49-53. doi: 10.1038/nature13527. Epub 2014 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland. ; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA. ; Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. ; 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland [3] Swiss Institute of Bioinformatics, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. ; Novartis Pharma AG, Institutes for Biomedical Research, Novartis Campus, CH-4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043012" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; DNA-Binding Proteins/agonists/antagonists & inhibitors/chemistry/metabolism ; Homeodomain Proteins/metabolism ; Humans ; Models, Molecular ; Multiprotein Complexes/agonists/antagonists & inhibitors/chemistry/metabolism ; Peptide Hydrolases/*chemistry/metabolism ; Protein Binding ; Structure-Activity Relationship ; Substrate Specificity ; Thalidomide/analogs & derivatives/*chemistry/metabolism ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/antagonists & inhibitors/*chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-04-01
    Description: The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 A resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cavadini, Simone -- Fischer, Eric S -- Bunker, Richard D -- Potenza, Alessandro -- Lingaraju, Gondichatnahalli M -- Goldie, Kenneth N -- Mohamed, Weaam I -- Faty, Mahamadou -- Petzold, Georg -- Beckwith, Rohan E J -- Tichkule, Ritesh B -- Hassiepen, Ulrich -- Abdulrahman, Wassim -- Pantelic, Radosav S -- Matsumoto, Syota -- Sugasawa, Kaoru -- Stahlberg, Henning -- Thoma, Nicolas H -- England -- Nature. 2016 Mar 31;531(7596):598-603. doi: 10.1038/nature17416.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. ; University of Basel, Petersplatz 10, 4003 Basel, Switzerland. ; Department of Cancer Biology, Dana-Farber Cancer Institute, LC-4312, 360 Longwood Avenue, Boston, Massachusetts 02215, USA. ; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02215, USA. ; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, 4058 Basel, Switzerland. ; Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. ; Novartis Pharma AG, Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland. ; Gatan R&D, 5974 W. Las Positas Boulevard, Pleasanton, California 94588, USA. ; Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan. ; Graduate School of Science, Kobe University, Kobe, 657-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029275" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Apoproteins/chemistry/metabolism/ultrastructure ; Binding Sites ; *Biocatalysis ; Carrier Proteins/chemistry/metabolism/ultrastructure ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Cullin Proteins/chemistry/metabolism/ultrastructure ; DNA Damage ; DNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Humans ; Kinetics ; Models, Molecular ; Multiprotein Complexes/chemistry/*metabolism/*ultrastructure ; Peptide Hydrolases/chemistry/*metabolism/*ultrastructure ; Protein Binding ; Ubiquitination ; Ubiquitins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Structural basis of lenalidomide-induced CK1alpha degradation by the CRL4(CRBN) ubiquitin ligase (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-02-26
    Description: Thalidomide and its derivatives, lenalidomide and pomalidomide, are immune modulatory drugs (IMiDs) used in the treatment of haematologic malignancies. IMiDs bind CRBN, the substrate receptor of the CUL4-RBX1-DDB1-CRBN (also known as CRL4(CRBN)) E3 ubiquitin ligase, and inhibit ubiquitination of endogenous CRL4(CRBN) substrates. Unexpectedly, IMiDs also repurpose the ligase to target new proteins for degradation. Lenalidomide induces degradation of the lymphoid transcription factors Ikaros and Aiolos (also known as IKZF1 and IKZF3), and casein kinase 1alpha (CK1alpha), which contributes to its clinical efficacy in the treatment of multiple myeloma and 5q-deletion associated myelodysplastic syndrome (del(5q) MDS), respectively. How lenalidomide alters the specificity of the ligase to degrade these proteins remains elusive. Here we present the 2.45 A crystal structure of DDB1-CRBN bound to lenalidomide and CK1alpha. CRBN and lenalidomide jointly provide the binding interface for a CK1alpha beta-hairpin-loop located in the kinase N-lobe. We show that CK1alpha binding to CRL4(CRBN) is strictly dependent on the presence of an IMiD. Binding of IKZF1 to CRBN similarly requires the compound and both, IKZF1 and CK1alpha, use a related binding mode. Our study provides a mechanistic explanation for the selective efficacy of lenalidomide in del(5q) MDS therapy. We anticipate that high-affinity protein-protein interactions induced by small molecules will provide opportunities for drug development, particularly for targeted protein degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petzold, Georg -- Fischer, Eric S -- Thoma, Nicolas H -- England -- Nature. 2016 Apr 7;532(7597):127-30. doi: 10.1038/nature16979. Epub 2016 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. ; University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26909574" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites/drug effects ; Casein Kinase Ialpha/chemistry/*metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Ikaros Transcription Factor/chemistry/metabolism ; Models, Molecular ; Protein Binding/drug effects ; Proteolysis/drug effects ; Structure-Activity Relationship ; Substrate Specificity/drug effects ; Thalidomide/*analogs & derivatives/chemistry/metabolism/pharmacology ; Ubiquitin-Protein Ligases/chemistry/*metabolism ; Ubiquitination/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    Electronic Resource
    Electronic Resource
    Proton release pathway in bacteriorhodopsin: Molecular dynamics and electrostatic calculations (1994)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 52 (1994), S. 33-56 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We use molecular dynamics, electrostatic, and quantumchemical calculations to discuss chromophore and protein structural changes as well as proton transfer pathways in the first half of the bacteriorhodopsin photocycle. A model for the molecular mechanism is presented, which accounts for the complex pH dependence of the proton release and uptake pattern found for the M intermediates. The results suggest that transient transfer of the Schiff base proton to a nearby tightly bound water molecule is the primary step, which is accompanyied by dissipation of free energy to the protein. From there, the energetically most favorable proton transfer is to aspartate D85. Arginine R82 is involved in the protein reorientation switch, which catalyzes the pKa reduction of glutamate E204. This residue is, therefore, identified as extracellular proton release group whose acid base equilibrium regulates the pH-dependent splitting of the photocycle. © 1994 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560520705
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Proton transfer to ubiquinone QB in the photosynthetic reaction center of Rps. Viridis: The role of electrostatic interactions (1993)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 48 (1993), S. 89-106 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Electrostatic calculations of the pKa of ionizable groups in the reaction center of Rhodopseudomonas (Rps.) viridis were carried out to investigate three possible mechanisms for proton transfer to the singly reduced acceptor ubiquinone QB. The program DelPhi, which solves the Poisson-Boltzmann equation given the distribution of charges and dielectric boundaries, was used to determine the electrostatic potential. The shift in pKa of the titratable residues in the QB binding pocket in response to the one-electron reduction and following protonation of QB was obtained from calculated interactions with the reaction field, background protein dipoles, charged cofactors, and other ionizable residues. A limited number of bound waters was also included in the computations as titrating sites. Their titration behavior was shown to be strongly coupled to neighboring ionizable sites. The results show that strong electrostatic interaction between the radical anion QB-· and a neighboring serine residue (SER L 223) as well as the protein environment stabilize a system in which the incoming proton is localized on serine and only shared in a hydrogen-bonding relationship with QB-·. These results hint to the possibility that actual proton transfer to QB-· only occurs after a second negative charge has been added to the system through transfer of a second electron either to the menaquinone QA, with formation of the QB-· QA-· system, or to QB-·, leading to the doubly reduced QB2-. This preposition is consistent with spectroscopical and electron nuclear double resonance (ENDOR) experimental results for bacterial reaction centers (RCs) failing to find evidence for the existence of the protonated semiquinone QBH·. © 1993 John Wiley & Sons, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560480712
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Reversible photochemistry in the α-subunit of phycoerythrocyanin: Characterization of chromophore and protein by electrostatic calculations (1993)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 48 (1993), S. 199-212 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We used a macroscopic dielectric model to study the effects of solvation and interaction between titratable and permanent partial charges on the protein conformational energy and the acid-base equilibria in the cyanobacterial photoreceptor phycoerythrocyanin, whose photoreversible photochromic response is attributed to a Z/E isomerization of the covalently bound tetrapyrrole chromophore. The calculations revealed the stabilization of the charged protonation state of the chromophore by a small set of strong local interactions. Although the protein is globular and water-soluble, the complex counterion structure has a striking similarity to the arrangement found for the photochemical active transmembrane protein bacteriorhodopsin. This could be attributed to the fact that the protonation site in the α-subunit of phycoerythrocyanin is buried in the interior of the protein. Due to the strong shielding from solvent, the interaction pattern is conserved upon a ground-state isomerization of the chromophore. The partial solvent exposure of the isomerization site resulted in a drastic influence of the chromophore configuration on the aqueous solvation energy of the protein. Implications for the sensitivity of the photochemistry to environmental factors and molecular binding are discussed. © 1993 John Wiley & Sons, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560480721
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    facet.materialart.
    Unknown
    A theoretical assessment of the O3/H2O interference problem in the detection of natural levels of OH via laser induced fluorescence (1981)
    In:  Other Sources
    Details
    Publication Date: 2019-06-28
    Description: Theoretical calculations are presented which estimate the possible magnitude of the O3/H2O derived OH interference signal resulting from the use of the laser-induced fluorescence technique in measuring natural levels of tropospheric OH. Critical to this new assessment has been the measurement of the nascent OH quantum state distribution resulting from the reaction O(1D) + H2O yields 2OH, and an assessment of the subsequent rotational relaxation of the OH species when formed in high k levels.
    Keywords: GEOPHYSICS
    Type: Geophysical Research Letters; 8; Jan. 198
    Format: text
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    NASA TECHNICAL REPORTS
  • 9
    facet.materialart.
    Unknown
    Energetic electrons and ions in the magnetosheath at low and medium latitudes - Prognoz 10 data (1992)
    In:  Other Sources
    Details
    Publication Date: 2019-08-28
    Description: We present a survey of Prognoz 10 energetic ion and electron observations at low and middle latitudes in the dayside magnetosheath. At low latitudes, peak fluxes are observed inside the magnetopause, whereas at middle latitudes the peak fluxes are generally observed in the magnetosheath at some distance from the magnetopause. Both electron and ion fluxes tend to be greater outside the dawnside magnetopause than outside the duskside magnetopause. The flux of energetic particles in the outer magnetosheath is almost invariably less than that within the inner magnetosheath. The observations indicate that leakage of magnetospheric particles is the dominant source of energetic particles in the magnetosheath, although Fermi acceleration at the bow shock is a possible subsidiary contributor to the population of ions with energies of about 15 keV.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 97; A10; p. 14,849-14,857.
    Format: text
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    NASA TECHNICAL REPORTS
  • 10
    facet.materialart.
    Unknown
    Possible leakage of energetic particles from the magnetosphere into the upstream region on June 7, 1985 (1990)
    In:  Other Sources
    Details
    Publication Date: 2019-07-12
    Description: Prognoz 10 observed a series of energetic ion (E not less than 10 KeV) and electron (E not less than 30 KeV) bursts whilst upstream of the dusk bow shock from 2000-2200 UT on June 7, 1985. The particles streamed away from the bow shock along the interplanetary magnetic field (IMF) during periods when the IMF connected the spacecraft to the bow shock/magnetosphere. Both ions and electrons were observed when the IMF connected the spacecraft to the subsolar bow shock, but only ions were observed when the IMF connected the spacecraft to the dusk bow shock. Simultaneous ground and magnetospheric observations are presented which indicate the onset of geomagnetic activity and an increase in magnetospheric energetic particle flux levels just prior to the series of particle bursts observed by Prognoz 10 upstream of the bow shock. The combined observations are consistent with a magnetospheric source for these upstream particle events.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 95; 20825-20
    Format: text
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    NASA TECHNICAL REPORTS
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...