Photo

Lan Huang

University of California, Irvine

Cross-Linking Mass Spectrometry Strategies for Delineating Protein Interactions and Structures

Abstract

Cross-linking mass spectrometry (XL-MS) have become a powerful structural tool for mapping protein-protein interactions (PPIs) and elucidating architectures of large protein complexes. In comparison to standard structural methods, XL-MS approaches offer distinct advantages due to speed, accuracy, sensitivity and versatility, especially for the study of heterogeneous and dynamic protein complexes. Despite its great potential, XL-MS analysis remains challenging due to inherent limitations in the analysis of cross-linked peptides. Here, we will present new developments in XL-MS technologies to facilitate the detection, identification and quantification of cross-linked peptides1,2. In addition, their applications in defining protein interactions and structures will be presented.

References:

[1] Kao, A. et al., MCP 2011.

[2] Yu, C. et al., Anal. Chem. 2018.

Biography

Dr.  Huang is Professor of Physiology & Biophysics in School of Medicine, University of California, Irvine. Her research focuses on developing novel, integrated mass spectrometry-based proteomic strategies to characterize dynamic proteomes of macromolecular protein complexes and understand their functions. Specifically, the Huang lab has developed novel cross-linking mass spectrometry (XL-MS) technologies by designing and synthesizing a series of sulfoxide-containing MS-cleavable cross-linkers (e.g. DSSO), and thus established a robust XL-MS platform enabling fast and accurate identification of cross-linked peptides. These XL-MS strategies have been successfully employed to determine architectures of protein complexes and define PPI landscapes at the systems-level in vitro and in vivo. Moreover, her lab has developed several quantitative cross-linking mass spectrometry strategies for comparative analysis of conformational changes in protein complexes.