A New Approach to Protein Structure and Interaction Research: Chemical Cross-linking in Combination With Mass Spectrometry

For any protein, its 3-D structure and interaction with other proteins are vital information for the understanding of its function. Traditionally, NMR and X-ray crystallography are employed to acquire such information at high resolution. However, application of these methods is limited because they are extremely demanding for protein purity and quantity, or protein size and crystalizability. Chemical cross-linking in combination with mass spectrometry(CXMS) is a novel technology developed over the past decade that complements the traditional methods with its many advantages such as high throughput, low cost and relaxed sample requirements. Here we review the various aspects of CXMS, including separation and enrichment techniques, characteristics of common cross-linkers, development of database-search tools for CXMS data,algorithms for validation of results, and application. The future development of CXMS is also discussed.