Abstract
Protein-protein interactions are essential for regulating almost all aspects of cellular functions. Many of these interactions are mediated by weak and transient protein domain-peptide binding, but they are often under-represented in high throughput screening of protein-protein interactions using techniques such as yeast two-hybrid and mass spectrometry. On the other hand, computational predictions and in vitro binding assays are valuable in providing clues of in vivo interactions. We present here a systematic approach that integrates computer modeling and a peptide microarray technology to identify binding peptides of the SH3 domain of the tyrosine kinase Abl1 in the human proteome. Our study provides a comprehensive list of candidate interacting partners for the Abl1 protein, among which the presence of numerous methyltransferases and RNA splicing proteins may suggest a novel function of Abl1 in chromatin remodeling and RNA processing. This study illustrates a powerful approach for integrating computational and experimental methods to detect protein interactions mediated by domain-peptide recognition.
Highlights
From the ‡Division of Biological Sciences and the ʈDepartment of Chemistry and Biochemistry, University of California, San Diego, California 92093-0359 and the ¶Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China
All 10-residue-long peptides in the UniProt database [7] were scored using the position-specific scoring matrix (PSSM)1 that we developed in a previous study [8]
Because the human Abl1 SH3 domain is completely conserved across these seven species, it is reasonable to assume that its interacting partners are highly conserved
Summary
From the ‡Division of Biological Sciences and the ʈDepartment of Chemistry and Biochemistry, University of California, San Diego, California 92093-0359 and the ¶Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China. High throughput technologies such as yeast two-hybrid and protein complex purification in conjunction with mass spectrometry have greatly facilitated the identification of protein-protein interactions. It will greatly enhance our understanding of the regulatory mechanism of Abl
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