SCIENCE@home

Multistate Structure Determination and Dynamics Analysis Reveals a Unique Ubiquitin-Recognition Mechanism in Ubiquitin C‑terminal Hydrolase

Mayu Okada,Yutaka Tateishi,Eri Nojiri,Tsutomu Mikawa,S. Rajesh,Hiroki Ogasa,Takumi Ueda,Hiromasa Yagi,Toshiyuki Kohno,Takanori Kigawa,Ichio Shimada,Peter Güntert,Yutaka Ito,T. Ikeya

Published 2025 in Journal of the American Chemical Society

ABSTRACT

Despite accumulating evidence that protein dynamics is indispensable for understanding the structural basis of biological activities, it remains challenging to visualize the spatial description of the dynamics and to associate transient conformations with their molecular functions. We have developed a new NMR protein structure determination method for the inference of multistate conformations using multiple types of NMR data, including paramagnetic NMR and residual dipolar couplings, as well as conventional NOEs. Integration of these data in the structure calculation permits delineating accurate ensemble structures of biomacromolecules. Applying the method to yeast ubiquitin hydrolase 1, we find large dynamics of its N-terminus (gating lid) and crossover loop surrounding the active site for ubiquitin-recognition and proteolysis. The N-terminus (gating lid) moves into and out of the crossover loop, suggesting their underlying functional significance. Our results, including those from biochemical analysis, show that large motion surrounding the active site contributes strongly to the efficiency of the enzymatic activity.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-41 of 41 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1