The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle

Klára Briknarová, Fariborz Nasertorabi, Marnie L. Havert, Ericka Eggleston, David W. Hoyt, Chenglong Li, Arthur J. Olson, Kristiina Vuori, Kathryn R. Ely

Research output: Contribution to journalArticlepeer-review

Abstract

p130cas (Crk-associated substrate) is a docking protein that is involved in assembly of focal adhesions and concomitant cellular signaling. It plays a role in physiological regulation of cell adhesion, migration, survival, and proliferation, as well as in oncogenic transformation. The molecule consists of multiple protein-protein interaction motifs, including a serine-rich region that is positioned between Crk and Src-binding sites. This study reports the first structure of a functional domain of Cas. The solution structure of the serine-rich region has been determined by NMR spectroscopy, demonstrating that this is a stable domain that folds as a four-helix bundle, a protein-interaction motif. The serine-rich region bears strong structural similarity to four-helix bundles found in other adhesion components like focal adhesion kinase, α-catenin, or vinculin. Potential sites for phosphorylation and interaction with the 14-3-3 family of cellular regulators are identified in the domain and characterized by site-directed mutagenesis and binding assays. Mapping the degree of amino acid conservation onto the molecular surface reveals a patch of invariant residues near the C terminus of the bundle, which may represent a previously unidentified site for protein interaction.

Original languageEnglish
Pages (from-to)21908-21914
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number23
DOIs
StatePublished - Jun 10 2005

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