6umb: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: '''Unreleased structure''' The entry 6umb is ON HOLD Authors: Munoz Sosa, C.J., Carrizo, M.E. Description: Crystal structure of TRIM7 B30.2 domain at 1.8 angstrom resolution [[Category... |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of TRIM7 B30.2 domain at 1.8 angstrom resolution== | |||
<StructureSection load='6umb' size='340' side='right'caption='[[6umb]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6umb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UMB FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6umb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6umb OCA], [https://pdbe.org/6umb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6umb RCSB], [https://www.ebi.ac.uk/pdbsum/6umb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6umb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRIM7_HUMAN TRIM7_HUMAN] E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of proinflammatory cytokines and type I interferon (By similarity). Plays also a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128).[UniProtKB:Q923T7]<ref>PMID:25851810</ref> <ref>PMID:32126128</ref> (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.<ref>PMID:32641828</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
TRIM7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1, the autoglucosyltransferase that initiates glycogen biosynthesis. A growing body of evidence indicates that TRIM7 plays an important role in cancer development, viral pathogenesis, and atherosclerosis, and thus represents a potential therapeutic target. TRIM family proteins share a multidomain architecture with a conserved N-terminal tripartite motif (TRIM) and a variable C-terminal domain. Human TRIM7 contains the canonical TRIM motif and a B30.2 domain at the C-terminus. In order to contribute to the understanding of the mechanism of action of TRIM7, we solved the X-ray crystal structure of its B30.2 domain (TRIM7(B30.2)) in two crystal forms at resolutions of 1.6 A and 1.8 A. TRIM7(B30.2) exhibits the typical B30.2 domain fold, consisting of two antiparallel beta-sheets of seven and six strands, arranged as a distorted beta-sandwich. Furthermore, two long loops partially cover the concave face of the beta-sandwich defined by the beta-sheet of six strands, thus forming a positively charged cavity. We used sequence conservation and mutational analyses to provide evidence of a putative binding interface for glycogenin-1. These studies showed that Leu423, Ser499 and Cys501 of TRIM7(B30.2), and the C-terminal 33 amino acids of glycogenin-1 are critical for this binding interaction. Molecular dynamics simulations also revealed that hydrogen bond and hydrophobic interactions play a major role in the stability of a modeled TRIM7(B30.2)-glycogenin-1 C-terminal peptide complex. These data provide useful information that can be used to target this interaction for the development of potential therapeutic agents. | |||
Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1.,Munoz Sosa CJ, Issoglio FM, Carrizo ME J Biol Chem. 2021 May 11:100772. doi: 10.1016/j.jbc.2021.100772. PMID:33989636<ref>PMID:33989636</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6umb" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Carrizo ME]] | |||
[[Category: Munoz Sosa CJ]] | |||
