Decoding Protein Dynamics in Cells Using Chemical Cross-Linking and Hierarchical Analysis.
Angew Chem Int Ed Engl
; 62(35): e202301345, 2023 08 28.
Article
in En
| MEDLINE
| ID: mdl-37406151
ABSTRACT
Protein dynamics play a crucial role in their diverse functions. The intracellular environment significantly influences protein dynamics, particularly for intrinsically disordered proteins (IDPs). To comprehensively capture structural information from various proteins within cells and characterize protein dynamics, chemical cross-linking mass spectrometry was employed. In this study, we introduce a hierarchical decoding strategy that enables the investigation of protein dynamics in vivo. Computational analysis based on distance restraints derived from cross-links is used to infer protein dynamics in cells. To facilitate this analysis, we leverage the prior structure obtained from AlphaFold2. By employing this strategy, we can characterize the full-length structure of multi-domain proteins taking into account their distinct dynamic features. Furthermore, by combining restraint sampling with an unbiased sampling and evaluation approach, we can provide a comprehensive description of the intrinsic motion of IDPs. Consequently, the hierarchical strategy we propose holds significant potential in advancing our understanding of the molecular mechanisms that undelie protein functions in cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Intrinsically Disordered Proteins
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2023
Document type:
Article
Affiliation country:
China