Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Linkage via K27 Bestows Ubiquitin Chains with Unique Properties Among Polyubiquitins

Published

Author(s)

Carlos A. Castaneda, Emma K. Dixon, Olivier Walker, Apurva Chaturvedi, Mark A. Nakasone, Joseph E. Curtis, Megan R. Reed, Susan T. Krueger, T. Ashton Cropp, David Fushman

Abstract

Polyubiquitination, a critical protein post-translational modification, signals fora diverse set of cellular events via the different isopeptide linkages formed between the C0terminus of one ubiquitin (Ub) and the ε}-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Using a nonenzymatic approach, we assembled di-Ubs (Ub2) comprised of every lysine linkage, except K63, and examined them biochemically and by using NMR. Of these, K27-Ub2 is unique as it is not cleaved by most deubiquitinases. As this remains the only structurally uncharacterized lysine-linkage, we extensively characterized the solution structures and dynamic of K27-Ub2 using NMR, small-angle neutron scattering (SANS), and in silico ensemble generation. Our structural that K27-Ub2 may be specifically recognized by UBA2 domain, a K48-selective receptor from proteasomal shuttle protein hhR23a, and binding studies validated this result. Our studies further highlight the potential power of determining function from elucidation of conformational states.
Citation
Structure
Volume
24
Issue
3

Keywords

protein structure, SANS, molecular dynamics, monte carlo

Citation

Castaneda, C. , Dixon, E. , Walker, O. , Chaturvedi, A. , Nakasone, M. , Curtis, J. , Reed, M. , Krueger, S. , Cropp, T. and Fushman, D. (2016), Linkage via K27 Bestows Ubiquitin Chains with Unique Properties Among Polyubiquitins, Structure, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=918792 (Accessed June 20, 2024)

Issues

If you have any questions about this publication or are having problems accessing it, please contact reflib@nist.gov.

Created February 29, 2016, Updated October 12, 2021