The role of the cysteine-rich region of the beta2 integrin subunit in the leukocyte function-associated antigen-1 (LFA-1, alphaLbeta2, CD11a/CD18) heterodimer formation and ligand binding.
The cysteine-rich region (CRR) of the beta2 integrin subunit was replaced by that of beta1 to give the chimera beta2NV1. Beta2NV1 can combine with alphaL to form a variant leukocyte-function-associated antigen (LFA)-1 on COS cell surface, suggesting that the specificity of the beta2 interaction with alphaL does not lie in the CRR. Unlike those expressing wild-type LFA-1, COS cells expressing alphaL beta2NV1 are constitutively active in intercellular adhesion molecule (ICAM)-1 adhesion. These results suggest that activation of LFA-1 involves the release of an intramolecular constraint, which is maintained, in part, by the authentic beta2 CRR.
Douglass
W A
WA
Department of Biochemistry, University of Oxford, UK.
Hyland
R H
RH
Buckley
C D
CD
Al-Shamkhani
A
A
Shaw
J M
JM
Scarth
S L
SL
Simmons
D L
DL
Law
S K
SK
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018821:CD18 Antigens / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D002448:Cell Adhesion; D003545:Cysteine / Q000502:physiology*; D019281:Dimerization; D000939:Epitopes / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D000939:Epitopes; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D003545:Cysteine