The first domain of intercellular adhesion molecule-1 (ICAM-1) binds to the leucocyte function-associated antigen-1 (LFA-1) I domain, which contains the principal ligand-binding site of this leucocyte integrin. Whether the function of the second domain is also to directly bind LFA-1 has been unclear. Our data show that mutation in the hydrophilic EF loop of ICAM-1 domain 2 resulted in impaired binding of the isolated I domain when compared with wild-type ICAM-1. LFA-1 on T-cells also binds with reduced affinity to this ICAM-1 mutant. A hybrid construct containing the first domain of vascular cell-adhesion molecule-1 joined to domains 2–5 of ICAM-1 was unable to bind to the I domain, showing that there is no direct interaction between the second domain of ICAM-1 and the I domain. This construct was also not bound by LFA-1 expressed in T-cells. Function-blocking monoclonal antibodies that map to domain 2 of ICAM-1, implicating this domain in ligand binding, were found to act indirectly. In summary our data suggest that the second domain of ICAM-1 has a role in maintaining the structure of the LFA-1 ligand-binding site in the first domain of ICAM-1 but does not appear to have a direct role in ligand binding.
Skip Nav Destination
Article navigation
October 2000
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
September 26 2000
The second domain of intercellular adhesion molecule-1 (ICAM-1) maintains the structural integrity of the leucocyte function-associated antigen-1 (LFA-1) ligand-binding site in the first domain
Paula STANLEY;
Paula STANLEY
*Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
Search for other works by this author on:
Alison MCDOWALL;
Alison MCDOWALL
*Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
Search for other works by this author on:
Paul A. BATES;
Paul A. BATES
†Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
Search for other works by this author on:
Joanna BRASHAW;
Joanna BRASHAW
*Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
Search for other works by this author on:
Nancy HOGG
Nancy HOGG
1
*Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
1To whom correspondence should be addressed (e-mail hogg@icrf.icnet.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 03 2000
Revision Received:
June 28 2000
Accepted:
July 24 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 351 (1): 79–86.
Article history
Received:
May 03 2000
Revision Received:
June 28 2000
Accepted:
July 24 2000
Citation
Paula STANLEY, Alison MCDOWALL, Paul A. BATES, Joanna BRASHAW, Nancy HOGG; The second domain of intercellular adhesion molecule-1 (ICAM-1) maintains the structural integrity of the leucocyte function-associated antigen-1 (LFA-1) ligand-binding site in the first domain. Biochem J 1 October 2000; 351 (1): 79–86. doi: https://doi.org/10.1042/bj3510079
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.