7te3
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of a Double Loop Deletion Mutant in gC1qR/C1qBP/HABP-1== | |
| + | <StructureSection load='7te3' size='340' side='right'caption='[[7te3]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7te3]] is a 1 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=7TE3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TE3 FirstGlance]. <br> | ||
| + | </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=7te3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7te3 OCA], [https://pdbe.org/7te3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7te3 RCSB], [https://www.ebi.ac.uk/pdbsum/7te3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7te3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/C1QBP_HUMAN C1QBP_HUMAN] Is believed to be a multifunctional and multicompartmental protein involved in inflammation and infection processes, ribosome biogenesis, regulation of apoptosis, transcriptional regulation and pre-mRNA splicing. At the cell surface is thought to act as an endothelial receptor for plasma proteins of the complement and kallikrein-kinin cascades. Putative receptor for C1q; specifically binds to the globular "heads" of C1q thus inhibiting C1; may perform the receptor function through a complex with C1qR/CD93. In complex with cytokeratin-1/KRT1 is a high affinty receptor for kininogen-1/HMWK. Can also bind other plasma proteins, such as coagulation factor XII leading to its autoactivation. May function to bind initially fluid kininogen-1 to the cell membrane. The secreted form may enhance both extrinsic and intrinsic coagulation pathways. It is postulated that the cell surface form requires docking with transmembrane proteins for downstream signaling which might be specific for a cell-type or response. By acting as C1q receptor is involved in chemotaxis of immature dendritic cells and neutrophils and is proposed to signal through CD209/DC-SIGN on immature dendritic cells, through integrin alpha-4/beta-1 during trophoblast invasion of the decidua, and through integrin beta-1 during endothelial cell adhesion and spreading. Signaling involved in inhibition of innate immune response is implicating the PI3K-AKT/PKB pathway. In mitochondrial translation may be involved in formation of functional 55S mitoribosomes; the function seems to involve its RNA-binding activity. May be involved in the nucleolar ribosome maturation process; the function may involve the exchange of FBL for RRP1 in the association with pre-ribosome particles. Involved in regulation of RNA splicing by inhibiting the RNA-binding capacity of SRSF1 and its phosphorylation. Is required for the nuclear translocation of splicing factor U2AF1L4. Involved in regulation of CDKN2A- and HRK-mediated apoptosis. Stabilizes mitochondrial CDKN2A isoform smARF. May be involved in regulation of FOXC1 transcriptional activity and NFY/CCAAT-binding factor complex-mediated transcription. In infection processes acts as an attachment site for microbial proteins, including Listeria monocytogenes internalin B and Staphylococcus aureus protein A. May play a role in antibacterial defense as it can bind to cell surface hyaluronan and inhibit Streptococcus pneumoniae hyaluronate lyase. Involved in replication of Rubella virus. May be involved in modulation of the immune response; ligation by HCV core protein is resulting in suppresion of interleukin-12 production in monocyte-derived dendritic cells. Involved in regulation of antiviral response by inhibiting DDX58- and IFIH1-mediated signaling pathways probably involving its association with MAVS after viral infection. Involved in HIV-1 replication, presumably by contributing to splicing of viral RNA.<ref>PMID:8662673</ref> <ref>PMID:8710908</ref> <ref>PMID:9461517</ref> <ref>PMID:10479529</ref> <ref>PMID:10022843</ref> <ref>PMID:10747014</ref> <ref>PMID:10722602</ref> <ref>PMID:11086025</ref> <ref>PMID:11859136</ref> <ref>PMID:12833064</ref> <ref>PMID:15243141</ref> <ref>PMID:16177118</ref> <ref>PMID:16140380</ref> <ref>PMID:17881511</ref> <ref>PMID:18676636</ref> <ref>PMID:19004836</ref> <ref>PMID:19164550</ref> <ref>PMID:20810993</ref> <ref>PMID:21536856</ref> <ref>PMID:21544310</ref> <ref>PMID:22700724</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The protein gC1qR/C1qBP/HABP-1 plays an essential role in mitochondrial biogenesis, but becomes localized at the cellular surface in numerous pathophysiological states. When this occurs on endothelial cells, surface-exposed gC1qR activates the classical pathway of complement. It also promotes assembly of a multi-protein complex comprised of coagulation factor XII (FXII), pre-kallikrein (PK), and high-molecular weight kininogen (HMWK) that activates the contact system and the kinin-generating system. Since surface-exposed gC1qR triggers intravascular inflammatory pathways, there is interest in identifying molecules that block gC1qR function. Here we further that objective by reporting the outcome of a structure/function investigation of gC1qR, its interactions with FXII, and the impact of a panel of monoclonal anti-gC1qR antibodies on FXII binding to gC1qR. Although deletion mutants have been used extensively to assess gC1qR function, none of these proteins have been characterized structurally. To that end, we determined a 2.2 A resolution crystal structure of a gC1qR mutant lacking both of its acidic loops, but which retained nanomolar-affinity binding to FXII and FXIIa. This structure revealed that the trimeric gC1qR assembly was maintained despite loss of roughly thirty residues. Characterization of a novel panel of anti-gC1qR monoclonal antibodies identified several with biochemical properties distinct from previously described antibodies, as well as one which bound to the first acidic loop of gC1qR. Intriguingly, we found that each of these antibodies could partly inhibit binding of FXII and FXIIa to gC1qR. Based on these results and previously published studies, we offer new perspectives for developing gC1qR inhibitors. | ||
| - | + | gC1qR/C1qBP/HABP-1: Structural Analysis of the Trimeric Core Region, Interactions With a Novel Panel of Monoclonal Antibodies, and Their Influence on Binding to FXII.,Zhang Y, Vontz AJ, Kallenberger EM, Xu X, Ploscariu NT, Ramyar KX, Garcia BL, Ghebrehiwet B, Geisbrecht BV Front Immunol. 2022 Jul 5;13:887742. doi: 10.3389/fimmu.2022.887742. eCollection , 2022. PMID:35865516<ref>PMID:35865516</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7te3" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Geisbrecht BV]] | ||
Revision as of 10:19, 14 December 2022
Crystal Structure of a Double Loop Deletion Mutant in gC1qR/C1qBP/HABP-1
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