Title : The structure of the two amino-terminal
domains of human
ICAM-1 suggests how it functions as a rhinovirus
receptor and as an
LFA-1 integrin ligand
Abstract :
- The normal function of human intercellular adhesion molecule-1 ( ICAM-1 ) is to provide adhesion between endothelial cells and leukocytes after injury or stress
- ICAM-1 binds to leukocyte function-associated antigen ( LFA-1 ) or macrophage-1 antigen ( Mac-1 )
- However, ICAM-1 is also used as a receptor by the major group of human rhinoviruses and is a catalyst for the subsequent viral uncoating during cell entry
- The three-dimensional atomic structure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determined to 2.2-A resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus- ICAM-1 complex
- Rhinovirus attachment is confined to the BC, CD, DE, and FG loops of the amino-terminal Ig-like domain (D1) at the end distal to the cellular membrane
- The loops are considerably different in structure to those of human ICAM-2 or murine ICAM-1 , which do not bind rhinoviruses
- There are extensive charge interactions between ICAM-1 and human rhinoviruses, which are mostly conserved in both major and minor receptor groups of rhinoviruses
- The interaction of ICAMs with LFA-1 is known to be mediated by a divalent cation bound to the insertion (I) -domain on the alpha chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs
- Domain D1 has been docked with the known structure of the I-domain
- The resultant model is consistent with mutational data and provides a structural framework for the adhesion between these molecules
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 0. ICAM-1, domains
- 4. ICAM-1, domains
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):