[NMR paper] High-Pressure NMR Spectroscopy Reveals Functional Sub-states of Ubiquitin and Ubiquitin-Like Proteins.

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High-Pressure NMR Spectroscopy Reveals Functional Sub-states of Ubiquitin and Ubiquitin-Like Proteins.

Related Articles High-Pressure NMR Spectroscopy Reveals Functional Sub-states of Ubiquitin and Ubiquitin-Like Proteins.

Subcell Biochem. 2015;72:199-214

Authors: Kitahara R

Abstract
High-pressure nuclear magnetic resonance (NMR) spectroscopy has revealed that ubiquitin has at least two high-energy states - an alternatively folded state N2 and a locally disordered state I - between the basic folded state N1 and totally unfolded U state. The high-energy states are conserved among ubiquitin-like post-translational modifiers, ubiquitin, NEDD8, and SUMO-2, showing the E1-E2-E3 cascade reaction. It is quite intriguing that structurally similar high-energy states are evolutionally conserved in the ubiquitin-like modifiers, and the thermodynamic stabilities vary among the proteins. To investigate atomic details of the high-energy states, a Q41N mutant of ubiquitin was created as a structural model of N2, which is 71*% populated even at atmospheric pressure. The convergent structure of the "pure" N2 state was obtained by nuclear Overhauser effect (NOE)-based structural analysis of the Q41N mutant at 2.5*kbar, where the N2 state is 97*% populated. The N2 state of ubiquitin is closely similar to the conformation of the protein bound to the ubiquitin-activating enzyme E1. The recognition of E1 by ubiquitin is best explained by conformational selection rather than by induced-fit motion.


PMID: 26174383 [PubMed - as supplied by publisher]



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