1xph

From Proteopedia

Structure of DC-SIGNR and a portion of repeat domain 8

PDB ID 1xph

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Structural highlights

1xph is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.41Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CLC4M_HUMAN Probable pathogen-recognition receptor involved in peripheral immune surveillance in liver. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. Probably recognizes in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens, including HIV-1 gp120, HIV-2 gp120, SIV gp120, ebolavirus glycoproteins, HCV E2, and human SARS coronavirus protein S. Is a receptor for ICAM3, probably by binding to mannose-like carbohydrates. Is presumably a coreceptor for the SARS coronavirus.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The dendritic cell-specific ICAM-3 non-integrin (DC-SIGN) and its close relative DC-SIGNR recognize various glycoproteins, both pathogenic and cellular, through the receptor lectin domain-mediated carbohydrate recognition. While the carbohydrate-recognition domains (CRD) exist as monomers and bind individual carbohydrates with low affinity and are permissive in nature, the full-length receptors form tetramers through their repeat domain and recognize specific ligands with high affinity. To understand the tetramer-based ligand binding avidity, we determined the crystal structure of DC-SIGNR with its last repeat region. Compared to the carbohydrate-bound CRD structure, the structure revealed conformational changes in the calcium and carbohydrate coordination loops of CRD, an additional disulfide bond between the N and the C termini of the CRD, and a helical conformation for the last repeat. On the basis of the current crystal structure and other published structures with sequence homology to the repeat domain, we generated a tetramer model for DC-SIGN/R using homology modeling and propose a ligand-recognition index to identify potential receptor ligands.

The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer.,Snyder GA, Colonna M, Sun PD J Mol Biol. 2005 Apr 15;347(5):979-89. PMID:15784257^[3]

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

References

↑ Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Eilering JB, Martin MP, Wu L, Martin TD, Viebig N, Knolle PA, KewalRamani VN, van Kooyk Y, Carrington M. A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med. 2001 Mar 19;193(6):671-8. PMID:11257134
↑ Pohlmann S, Soilleux EJ, Baribaud F, Leslie GJ, Morris LS, Trowsdale J, Lee B, Coleman N, Doms RW. DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2670-5. PMID:11226297 doi:10.1073/pnas.051631398
↑ Snyder GA, Colonna M, Sun PD. The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer. J Mol Biol. 2005 Apr 15;347(5):979-89. PMID:15784257 doi:http://dx.doi.org/10.1016/j.jmb.2005.01.063