5UJL

Representative 1-conformer ensembles of K27-linked Ub2 from RDC data

Summary for 5UJL

• Entry DOI: 10.2210/pdb5ujl/pdb
• NMR Information: BMRB: 30234
• Descriptor: Ubiquitin (1 entity in total)
• Functional Keywords: diubiquitin, k27-linkage, post-translational modification, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 17153.66

Authors

Castaneda, C.A.,Fushman, D. (deposition date: 2017-01-18, release date: 2017-10-25, Last modification date: 2024-05-15)

Primary citation

Castaneda, C.A.,Dixon, E.K.,Walker, O.,Chaturvedi, A.,Nakasone, M.A.,Curtis, J.E.,Reed, M.R.,Krueger, S.,Cropp, T.A.,Fushman, D.
Linkage via K27 Bestows Ubiquitin Chains with Unique Properties among Polyubiquitins.
Structure, 24:423-436, 2016

PubMed 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 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 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.

PubMed: 26876099
DOI: 10.1016/j.str.2016.01.007

Experimental method

SOLUTION NMR