A Tyrosine Reactive Cross-Linker for Probing Protein 3D Structures

ABSTRACT: Cross-linking mass spectrometry (XL-MS) has made significant progress in understanding the structure of protein and elucidating architectures of larger protein complexes. Current XL-MS applications are limited to targeting lysine, glutamic acid, aspartic acid, and cysteine residues. There remains a need for the development of novel cross-linkers enabling selectively target other amino-acid residues in proteins. Here, a novel simple cross-linker, namely [4,4'-(disulfanediylbis(ethane-2,1-diyl)) bis(1,2,4-triazolidine-3,5-dione)] (DBB), has been designed, synthesized, and characterized. This cross-linker can react selectively with tyrosine residues in protein through electrochemical click reaction. Upon tandem mass spectrometry, the DBB cross-links produced the characteristic fragments, thus permitting the simplified data analysis and accurate identification for the cross-linked products. This is the first time developing a cross-linker for targeting tyrosine residue on protein without using photoirradiation or metal catalyst. This strategy might potentially be used as a complementary tool for XL-MS to probe protein 3D structures, protein complexes, and protein-protein interaction.

ORGANISM(S): Homo Sapiens

SUBMITTER: Ming Li  

PROVIDER: PXD022121 | iProX | Thu Oct 22 00:00:00 BST 2020

REPOSITORIES: iProX