4fmf

From Proteopedia

Crystal structure of human nectin-1 full ectodomain (D1-D3)

Structural highlights

4fmf is a 4 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 3.2Å
Ligands:	FMT, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NECT1_HUMAN Cleft lip/palate;Isolated cleft lip;Cleft lip and alveolus;Cleft lip/palate-ectodermal dysplasia syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

NECT1_HUMAN Promotes cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions have been detected between NECTIN1 and NECTIN3 and between NECTIN1 and NECTIN4. Has some neurite outgrowth-promoting activity.^[1] (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1, herpes simplex virus 2/HHV-2, and pseudorabies virus/PRV.^[2] ^[3]

Publication Abstract from PubMed

Nectins are immunoglobulin superfamily glycoproteins that mediate intercellular adhesion in many vertebrate tissues. Homophilic and heterophilic interactions between nectin family members help mediate tissue patterning. We determined the homophilic binding affinities and heterophilic specificities of all four nectins and the related protein nectin-like 5 (Necl-5) from human and mouse, revealing a range of homophilic interaction strengths and a defined heterophilic specificity pattern. To understand the molecular basis of their adhesion and specificity, we determined the crystal structures of natively glycosylated full ectodomains or adhesive fragments of all four nectins and Necl-5. All of the crystal structures revealed dimeric nectins bound through a stereotyped interface that was previously proposed to represent a cis dimer. However, conservation of this interface and the results of targeted cross-linking experiments showed that this dimer probably represents the adhesive trans interaction. The structure of the dimer provides a simple molecular explanation for the adhesive binding specificity of nectins.

Nectin ectodomain structures reveal a canonical adhesive interface.,Harrison OJ, Vendome J, Brasch J, Jin X, Hong S, Katsamba PS, Ahlsen G, Troyanovsky RB, Troyanovsky SM, Honig B, Shapiro L Nat Struct Mol Biol. 2012 Aug 19. doi: 10.1038/nsmb.2366. PMID:22902367^[4]

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

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Citations

reviews cite this structure

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References

↑ Di Giovine P, Settembre EC, Bhargava AK, Luftig MA, Lou H, Cohen GH, Eisenberg RJ, Krummenacher C, Carfi A. Structure of herpes simplex virus glycoprotein d bound to the human receptor nectin-1. PLoS Pathog. 2011 Sep;7(9):e1002277. Epub 2011 Sep 29. PMID:21980294 doi:10.1371/journal.ppat.1002277
↑ Lopez M, Eberle F, Mattei MG, Gabert J, Birg F, Bardin F, Maroc C, Dubreuil P. Complementary DNA characterization and chromosomal localization of a human gene related to the poliovirus receptor-encoding gene. Gene. 1995 Apr 3;155(2):261-5. PMID:7721102
↑ Warner MS, Geraghty RJ, Martinez WM, Montgomery RI, Whitbeck JC, Xu R, Eisenberg RJ, Cohen GH, Spear PG. A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus. Virology. 1998 Jun 20;246(1):179-89. PMID:9657005 doi:http://dx.doi.org/10.1006/viro.1998.9218
↑ Harrison OJ, Vendome J, Brasch J, Jin X, Hong S, Katsamba PS, Ahlsen G, Troyanovsky RB, Troyanovsky SM, Honig B, Shapiro L. Nectin ectodomain structures reveal a canonical adhesive interface. Nat Struct Mol Biol. 2012 Aug 19. doi: 10.1038/nsmb.2366. PMID:22902367 doi:http://dx.doi.org/10.1038/nsmb.2366