Structural highlights
Disease
[PVRL1_HUMAN] Zlotogora-Ogur syndrome;Cleft lip with or without cleft palate. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[PVRL1_HUMAN] Promotes cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions have been detected between PVRL1/nectin-1 and PVRL3/nectin-3 and between PVRL1/nectin-1 and PVRL4/nectin-4. Functions as an entry receptor for herpes simplex virus and pseudorabies virus.[1]
Publication Abstract from PubMed
Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 A resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting beta-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region.
Structure of herpes simplex virus glycoprotein d bound to the human receptor nectin-1.,Di Giovine P, Settembre EC, Bhargava AK, Luftig MA, Lou H, Cohen GH, Eisenberg RJ, Krummenacher C, Carfi A PLoS Pathog. 2011 Sep;7(9):e1002277. Epub 2011 Sep 29. PMID:21980294[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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