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Linkage via K27 Bestows Ubiquitin Chains with Unique Properties among Polyubiquitins.


ABSTRACT: Polyubiquitination, a critical protein post-translational modification, signals for a diverse set of cellular events via the different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the ?-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. We assembled di-ubiquitins (Ub2) comprising every lysine linkage and examined them biochemically and structurally. Of these, K27-Ub2 is unique as it is not cleaved by most deubiquitinases. As this remains the only structurally uncharacterized lysine linkage, we comprehensively examined the structures and dynamics of K27-Ub2 using nuclear magnetic resonance, small-angle neutron scattering, and in silico ensemble modeling. Our structural data provide insights into the functional properties of K27-Ub2, in particular that K27-Ub2 may be specifically recognized by K48-selective receptor UBA2 domain from proteasomal shuttle protein hHR23a. Binding studies and mutagenesis confirmed this prediction, further highlighting structural/recognition versatility of polyubiquitins and the potential power of determining function from elucidation of conformational ensembles.

SUBMITTER: Castaneda CA 

PROVIDER: S-EPMC4787624 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Linkage via K27 Bestows Ubiquitin Chains with Unique Properties among Polyubiquitins.

Castañeda Carlos A CA   Dixon Emma K EK   Walker Olivier O   Chaturvedi Apurva A   Nakasone Mark A MA   Curtis Joseph E JE   Reed Megan R MR   Krueger Susan S   Cropp T Ashton TA   Fushman David D  

Structure (London, England : 1993) 20160211 3


Polyubiquitination, a critical protein post-translational modification, signals for a diverse set of cellular events via the different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the ɛ-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. We assembled di-ubiquitins (Ub2) comprising every lysine linkage and examined them biochemically and structurally. Of these, K27-Ub2 is unique as it is not cleaved by most deubiquitinases. As this remains the only structur  ...[more]

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