Proteome-wide detection of Abl1 SH3-binding peptides by integrating computational prediction and peptide microarray.
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.
Division of Biological Sciences, San Diego, California 92093-0359.
Zheng
Z
Xu
Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Tingjun
T
Hou
Department of Chemistry and Biochemistry, University of California, San Diego, California 92093-0359.
Nan
N
Li
Division of Biological Sciences, San Diego, California 92093-0359.
Yang
Y
Xu
Department of Chemistry and Biochemistry, University of California, San Diego, California 92093-0359. Electronic address: wei-wang@ucsd.edu.
Wei
W
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003198:Computer Simulation; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D040081:Protein Array Analysis; D011485:Protein Binding; D020543:Proteome; D018909:src Homology Domains
C513733:ABI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D003598:Cytoskeletal Proteins; D010455:Peptides; D020543:Proteome