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3x0e

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Revision as of 12:10, 12 April 2017

Crystal structure of the ectodomain of human CD81 large extracellular loop (hCD81-LEL)

Structural highlights

3x0e is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1g8q, 1iv5, 3x0f, 3x0g
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CD81_HUMAN] Defects in CD81 are the cause of immunodeficiency common variable type 6 (CVID6) [MIM:613496]; also called antibody deficiency due to CD81 defect. CVID6 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.^[1]

Function

[CD81_HUMAN] May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV.

Publication Abstract from PubMed

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases; however, HCV vaccine remains unavailable to date. One main obstacle is the lack of an efficient small animal model. Cluster of differentiation 81 (CD81) is an essential entry coreceptor for HCV species specificity to human, though the underlying mechanisms are yet to be fully elucidated. We performed structural, biophysical, and virologic studies on HCV nonpermissive CD81s from mouse and African green monkey [mouse cluster of differentiation 81 (mCD81) and African green monkey cluster of differentiation 81 (agmCD81)] and compared with human cluster of differentiation 81 (hCD81). We discovered an intramolecular hydrogen bond (Gln188-Nepsilon2-H: Glu196-Oepsilon2, 2 A, 124 degrees ) within the large extracellular loop (LEL) of mCD81 and a salt bridge (Lys188-Nzeta: Asp196-Odelta2, 2.4 A) within agmCD81-LEL between 188-196 residues. This structural feature is missing in hCD81. We demonstrated that the introduction of a single 188-196 bond to hCD81 impaired its binding affinity to HCV envelope glycoprotein 2 (HCV E2) and significantly decreased HCV pseudoviral particle (HCVpp) entry efficiency (4.92- to 8.42-fold) and cell culture-grown HCV (HCVcc) infectivity (4.55-fold), despite the availability of Phe186. For HCV nonpermissive CD81s, the introduction of Phe186 by Leu186F substitution alone was insufficient to confer HCV permissiveness. The disruption of the original 188-196 bond and Leu186F substitution were both required for potent binding to HCV E2 HCVpp entry efficiency and HCVcc infectivity. Our structural and biophysical analyses suggest that the intramolecular 188-196 bond restricts the intrinsic conformational dynamics of D-helix of CD81-LEL, which is essential for HCV entry, thus impairs HCV permissiveness. Our findings reveal a novel molecular determinant for HCV entry in addition to the well-characterized Phe186 and provide further guideline for selecting an HCV small animal model.-Yang, W., Zhang, M., Chi, X., Liu, X., Qin, B., Cui, S. An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry.

An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry.,Yang W, Zhang M, Chi X, Liu X, Qin B, Cui S FASEB J. 2015 Jun 26. pii: fj.15-272880. PMID:26116703^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ van Zelm MC, Smet J, Adams B, Mascart F, Schandene L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. 2010 Apr;120(4):1265-74. doi: 10.1172/JCI39748. Epub 2010 Mar 8. PMID:20237408 doi:10.1172/JCI39748
↑ Yang W, Zhang M, Chi X, Liu X, Qin B, Cui S. An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry. FASEB J. 2015 Jun 26. pii: fj.15-272880. PMID:26116703 doi:http://dx.doi.org/10.1096/fj.15-272880

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3x0e"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the ectodomain of human CD81 large extracellular loop (hCD81-LEL)==
 <StructureSection load='3x0e' size='340' side='right' caption='[[3x0e]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1g8q|1g8q]], [[1iv5|1iv5]], [[3x0f|3x0f]], [[3x0g|3x0g]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3x0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x0e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3x0e RCSB], [http://www.ebi.ac.uk/pdbsum/3x0e PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3x0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x0e OCA], [http://pdbe.org/3x0e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3x0e RCSB], [http://www.ebi.ac.uk/pdbsum/3x0e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3x0e ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3x0e" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3x0e

From Proteopedia

Revision as of 12:10, 12 April 2017

Crystal structure of the ectodomain of human CD81 large extracellular loop (hCD81-LEL)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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