PMID: 21980294

 

    Legend: Gene, Sites

Title : Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1

Abstract :

1. 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
2. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells
3. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution
4. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor
5. 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
6. Phenylalanine 129 , at the tip of the loop connecting β-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
7. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry
8. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions
9. 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

Output (sent_index, trigger, protein, sugar, site):

• 0. glycoprotein, , glycoprotein D, -, -
• 1. glycoprotein, , glycoprotein D, -, -

Output(Part-Of) (sent_index, protein, site):

• 4. HVEM receptor, site
• 4. gD, site
• 4. nectin-1, site
• 5. nectin-1, Ig-domain
• 6. gD, residues in
• 9. gD C, region

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
nectin-1	5818	3,4,5,6,7,8
HVEM	8764	6
Nectin-1	5818	2
HVEM receptor	8764	4
gD C	8034	9
glycoprotein D	2532	0,1