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A hierarchical strategy to decipher protein dynamics in vivo with chemical cross-linking mass spectrometry

Zhang, B.; Gong, Z.; Zhao, L.; An, Y.; Gao, H.; Chen, J.; Liang, Z.; Liu, M.; Zhang, Y.; Zhao, Q.; Zhang, L.

2023-03-21 cell biology
10.1101/2023.03.21.533582 bioRxiv
Show abstract

Protein dynamics are essential for their various functions. Meanwhile, the intracellular environment would affect protein structural dynamics, especially for the intrinsically disordered proteins (IDPs). Chemical cross-linking mass spectrometry (CXMS) can unbiasedly capture the protein conformation information in cells and can also represent the protein dynamics. Here, we proposed a hierarchy deciphering strategy for protein dynamics in vivo. With the prior structure from AlphaFold2, the steady local conformation can be extensively evaluated. On this basis, the full-length structure of multi-domain proteins with various dynamic features can be characterized using CXMS. Furthermore, the complementary strategy with unbiased sampling and distance-constrained sampling enables an objective description of the intrinsic motion of the IDPs. Therefore, the hierarchy strategy we presented herein could help us better understand the molecular mechanisms of protein functions in cells.

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