4UN2

Crystal structure of the UBA domain of Dsk2 in complex with Ubiquitin

Summary for 4UN2

• Entry DOI: 10.2210/pdb4un2/pdb
• Descriptor: UBIQUITIN, UBIQUITIN DOMAIN-CONTAINING PROTEIN DSK2 (3 entities in total)
• Functional Keywords: protein binding, ubiquitin-associated domain, protein degradation
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Ubiquitin: Cytoplasm (By similarity): P0CG48; Nucleus (Probable): P48510
• Total number of polymer chains: 2
• Total formula weight: 13921.64

Authors

Michielssens, S.,Peters, J.H.,Ban, D.,Pratihar, S.,Seeliger, D.,Sharma, M.,Giller, K.,Sabo, T.M.,Becker, S.,Lee, D.,Griesinger, C.,de Groot, B.L. (deposition date: 2014-05-23, release date: 2014-08-27, Last modification date: 2024-01-10)

Primary citation

Michielssens, S.,Peters, J.H.,Ban, D.,Pratihar, S.,Seeliger, D.,Sharma, M.,Giller, K.,Sabo, T.M.,Becker, S.,Lee, D.,Griesinger, C.,De Groot, B.L.
A Designed Conformational Shift to Control Protein Binding Specificity.
Angew.Chem.Int.Ed.Engl., 53:10367-, 2014

PubMed Abstract: In a conformational selection scenario, manipulating the populations of binding-competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground-state ensemble between open and closed substates that have a similar population in the wild-type protein. Binding affinities determined by NMR titration experiments agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to alter ubiquitin's binding specificity and hence its function. Thus, we present a novel route towards designing specific binding by a conformational shift through exploiting the fact that conformational selection depends on the concentration of binding-competent substates.

PubMed: 25115701
DOI: 10.1002/ANIE.201403102

Experimental method

X-RAY DIFFRACTION (1.51 Å)