The structure of the two amino-terminal domains of human intercellular adhesion molecule-1 suggests how it functions as a rhinovirus receptor

Jordi Bella, Prasanna R. Kolatkar, Christopher W. Marlor, Jeffrey M. Greve, Michael G. Rossmann

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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-l). However, ICAM-1 is also utilized 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 cryo-electron microscopy reconstruction of a rhinovirus-ICAM-1 complex. Rhinovirus attachment is confined to the BC, CD, DE and FG loops of the amino-terminal immunoglobulin-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 I-(insertion) domain on the α chain of LFA-1 and the carboxy 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. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)107-117
Number of pages11
JournalVirus Research
Volume62
Issue number2
DOIs
Publication statusPublished - 1 Aug 1999

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Keywords

  • Human rhinoviruses
  • ICAM-1 structure
  • Receptor interaction

ASJC Scopus subject areas

  • Cancer Research
  • Virology
  • Infectious Diseases

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