Structurally homologous ligand binding of integrin Mac-1 and viral glycoprotein C receptors.
Three spatially distant surface loops were found to mediate the interaction of the coagulation protein factor X with the leukocyte integrin Mac-1. This interacting region, which by computational modeling defines a three-dimensional macromotif in the catalytic domain, was also recognized by glycoprotein C (gC), a factor X receptor expressed on herpes simplex virus (HSV)-infected endothelial cells. Peptidyl mimicry of each loop inhibited factor X binding to Mac-1 and gC, blocked monocyte generation of thrombin, and prevented monocyte adhesion to HSV-infected endothelium. These data link the ligand recognition of Mac-1 to established mechanisms of receptor-mediated vascular injury.
Altieri
D C
DC
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Etingin
O R
OR
Fair
D S
DS
Brunck
T K
TK
Geltosky
J E
JE
Hajjar
D P
DP
Edgington
T S
TS
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002460:Cell Line; D005170:Factor X / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000378:metabolism*
D008024:Ligands; D016177:Macrophage-1 Antigen; D010455:Peptides; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; D005170:Factor X