Finding Chimeras: a Bioinformatics Strategy for Identification of Cross-linked Peptides

• Published in: Molecular & cellular proteomics Vol. 9; no. 1; pp. 25 - 31
• Main Authors: Chu, Feixia, Baker, Peter R., Burlingame, Alma L., Chalkley, Robert J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2010; American Society for Biochemistry and Molecular Biology; The American Society for Biochemistry and Molecular Biology
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Computational Biology - methods; Cross-Linking Reagents - chemistry; Crystallography, X-Ray; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Molecular Structure; Mutation; Periplasmic Proteins - chemistry; Periplasmic Proteins - genetics; Protein Binding; Protein Conformation; Protein Multimerization; Protein Structure, Quaternary; Protein Structure, Tertiary; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Software
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M800555-MCP200

Chemical cross-linking, followed by identification of the cross-linked residues, is a powerful approach to probe the topologies and interacting surfaces of protein assemblies. In this work, we demonstrate a new bioinformatics approach using multiple program modules within the software package “Protein Prospector” that greatly facilitates the discovery of cross-linked peptides in chemical cross-linking studies. Examples are given for how this approach has been used for defining interfaces in heterodimeric and homodimeric protein complexes, both of which provide results in close agreement with crystal structures, verifying the reliability of the approach.