Critical Residues for Ligand Binding in an I Domain-like Structure of the Integrin β1 Subunit*
- ‡ To whom correspondence should be addressed: Dept. of Vascular Biology, VB-1, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: 619-784-7122; Fax: 619-784-7323; E-mail: takada{at}scripps.edu.
Abstract
Several integrin α subunits have an inserted sequence of about 200 residues (the I or A domain) that is critical for ligand interactions. The presence of an I domain-like structure within the integrin β subunit has been proposed based on the similarity of the hydropathy profiles and the homology of sequences between the α and β subunits. This study was designed to determine whether the region of the β1 subunit that includes residues 101-335 has the characteristics of an I domain. We found novel critical residues for ligand binding (Ser-132, Asn-224, Asp-226, Glu-229, Asp-233, Asp-267, and Asp-295, in addition to the previously reported Asp-130) using site-directed mutagenesis. The critical residues for ligand binding are located in several of loop structures of the region (or in a potential loop between an α helix and a β strand), which have been predicted using multiple secondary structure prediction methods. The data suggest that the β subunit has multiple disrupted critical oxygenated residues for ligand binding similar to those found in the α I domain.
Footnotes
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↵* This work was supported by National Institutes of Health Grants GM47157 and GM49899. This is publication 9766-VB 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.
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↵1 The abbreviations used are:
- mAb
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monoclonal antibody
- FN
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fibronectin
- PBS
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phosphate-buffered saline
- CHO
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Chinese hamster ovary
- FITC
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fluorescein isothiocyanate.
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- Received March 5, 1996.
- Revision received June 4, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
