Molecular Requirements for Assembly and Function of a Minimized Human Integrin αIIbβ3

doi:10.1074/jbc.271.48.30544

Molecular Requirements for Assembly and Function of a Minimized Human Integrin α_IIbβ₃*

From the Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis of the Department of Molecular and Experimental Medicine and the Department of Vascular Biology of The Scripps Research Institute, La Jolla, California 92017

^∥ To whom correspondence and requests for materials should be addressed:
Dept. of Molecular and Experimental Medicine, Maildrop SBR13, Rm. SR11, 10550 North Torrey Pines Rd., La Jolla, CA 92017.
Tel.: 619-784-2668; Fax: 619-784-2174.

↵^‡ Present address: The Second Dept. of Internal Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan.
↵^§ Present address: DADE International, Inc., P. O. Box 520672, Miami, FL 33152-0672.

Abstract

Integrin subunit compatibility within and between species plays a major role in heterodimer assembly and ligand specificity. As an example, human α_IIb pairs only with human β₃ and does not assemble a heterodimer with β₃ from other species. We use interspecies subunit chimeras to identify molecular requirements for subunit compatibility and show that species-restricted heterodimer assembly depends on a unique hexapeptide VGSDNH in an extended loop of the hypothetical human β₃ MIDAS domain. This allows us to express α_IIb(1-233) and β₃(111-318) as a soluble, mini-integrin that retains RGD-dependent ligand recognition. Thus, in the case of one integrin, α_IIbβ₃, the molecular requirements for integrin subunit compatibility and ligand recognition are intimately related.

Footnotes

↵* This study was supported by Grant HL-46979 from NHLBI, National Institutes of Health, a grant from the Gustavus and Louise Pfeiffer Research Foundation (Redlands, CA) (awarded to T. J. K.), and an individual National Research Service Award (held by B. S. M.). This is manuscript number 10066-MEM from The Scripps Research Institute. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviation used is:

PVDF

polyvinyl pyrolidine filters.
- Received July 29, 1996.
- Revision received September 19, 1996.