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Sci. STKE, 9 September 2003
Vol. 2003, Issue 199, p. tw349
[DOI: 10.1126/stke.2003.199.tw349]

EDITORS' CHOICE

PROTEIN INTERACTIONS New SH3 Recognition Motif

Proteins of the CIN85 and CMS adaptor family contain SH3 domains, which are proline recognition sequences mediating protein interactions. However, the binding sites within known CIN85 target proteins do not appear to be canonical P-X-X-P motifs. Kurakin et al. used target-assisted iterative screening (TAIS) to identify sequences preferred by the first, second, and third SH3 domains of CIN85. Although there were variations in residues tolerated in the "X" positions, each of the CIN85 SH3 domains recognized the sequence P-X-(P or A)-X-X-R. Homology searches for the CIN85 SH3 recognition motif showed many potential new partners and confirmed the presence of this motif in known CIN85 partners. Four of the newly identified potential partners were investigated further to confirm an interaction with CIN85. Interaction with two of these, synaptojanin 1 and the kinase PAK2, was detected in mouse brain lysates by glutathione S-transferase (GST) fusion protein pull-down assay and by Far Western analysis; Z0-2 and TAFII70 were only detected in a GST pull-down assay. This approach and the results demonstrate (i) that TAIS is an effective method for identifying binding motifs, which can then be used to identify new partners, (ii) that the CIN85 SH3 domain recognizes a noncanonical proline sequence, and (iii) that CIN85 may also interact with synaptojanin 1, PAK2, ZO-2, and TAFII70, which suggests additional functions.

A. V. Kurakin, S. Wu, D. E. Bredesen, Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening. J. Biol. Chem. 278, 34102-34109 (2003). [Abstract] [Full Text]

Citation: New SH3 Recognition Motif. Sci. STKE 2003, tw349 (2003).



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