Evolutionary Role of Water-Accessible Cavities in Src Homology 2 (SH2) Domains

被引:3
作者
de Oliveira, Guilherme A. P. [1 ]
Arruda, Hiam R. S. [1 ]
de Andrade, Guilherme C. [1 ]
Silva, Jerson L. [1 ]
机构
[1] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo Meis, Natl Inst Sci & Technol Struct Biol & Bioimaging, Natl Ctr Nucl Magnet Resonance Jiri Jonas, BR-21941902 Rio De Janeiro, RJ, Brazil
关键词
C-ABL; PROTEIN HYDRATION; NMR-SPECTROSCOPY; HYDROGEN-BONDS; DYNAMICS; BINDING; SYSTEM; CRYSTALLOGRAPHY; AUTOINHIBITION; BIOLOGY;
D O I
10.1021/acs.jpcb.2c05409
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Protein excited states are fundamental in the understanding of biological function, despite the fact they are hardly observed using traditional biophysical methodologies. Pressure perturbation coupled with nuclear magnetic resonance (NMR) spectroscopy is a powerful physicochemical tool to glance at these low-populated high-energy states on a residue-by-residue basis and underpin mechanistic insights into protein function-alities. Here we performed pressure titrations using NMR spectroscopy and relaxation dispersion experiments to identify the low-lying energetic states of the c-Abl SH2 domain. By showing that the SH2 excited state contains a hydrated hydrophobic cavity, fast-exchange motions, and highly conserved residues facing the water-accessible hole, we discuss the implications of water-protein interactions in SH2 modules achieving high-affinity binding and promiscuous phospho-Tyr peptide recognition.
引用
收藏
页码:8689 / 8698
页数:10
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