Work

An isolated, surface-expressed I domain of the integrin αLβ2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond

Year: 2001

Type: article

Abstract: We introduced disulfide bonds to lock the integrin alphaLbeta2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing alphaLbeta2 heterodimers containing locked-open but not locked-closed or wild-type I domains constitutively adhered to intercellular adhesion molecule-1 (ICAM-1) substrates. Locking the I domain closed abolished constitutive and activatable adhesion. The isolated locked-open I domain bound as well as the activated alphaLbeta2 heterodimer, and binding was abolished by reduction of the disulfide. Lovastatin, which binds under the conformationally mobile C-terminal alpha-helix of the I domain, inhibited binding to ICAM-1 by alphaLbeta2 with wild-type, but not locked-open I domains. These data establish the importance of conformational change in the alphaL I domain for adhesive function and show that this domain is sufficient for full adhesive activity.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.041606398

Authors: Chafen Lu, Motomu Shimaoka, Mazen Ferzly, Claus Oxvig, Junichi Takagi, Timothy A. Springer

Institution: Harvard University

Language: English

Topic: Cell Adhesion Molecules Research

Subfield: Immunology and Allergy

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: Cancer Research Institute, National Institutes of Health, National Cancer Institute

Awards: G2456329664, Lymphocyte Function Associated Antigens, LYMPHOCYTE FUNCTION ASSOCIATED ANTIGENS, G9000169461