2m0x

Solution structure of U14Ub1, an engineered ubiquitin variant with increased affinity for USP14

spinqualitylabelsall models 2m0x Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2m0x is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Ubiquitin is a highly conserved eukaryotic protein that interacts with a diverse set of partners to act as a cellular signaling hub. Ubiquitin's conformational flexibility has been postulated to underlie its multifaceted recognition. Here we use computational and library-based means to interrogate core mutations that modulate the conformational dynamics of human ubiquitin. These ubiquitin variants exhibit increased affinity for the USP14 deubiquitinase, with concomitantly reduced affinity for other deubiquitinases. Strikingly, the kinetics of conformational motion are dramatically slowed in these variants without a detectable change in either the ground state fold or excited state population. These variants can be ligated into substrate-linked chains in vitro and in vivo but cannot solely support growth in eukaryotic cells. Proteomic analyses reveal nearly identical interaction profiles between WT ubiquitin and the variants but identify a small subset of altered interactions. Taken together, these results show that conformational dynamics are critical for ubiquitin-deubiquitinase interactions and imply that the fine tuning of motion has played a key role in the evolution of ubiquitin as a signaling hub. Conformational dynamics control ubiquitin-deubiquitinase interactions and influence in vivo signaling.,Phillips AH, Zhang Y, Cunningham CN, Zhou L, Forrest WF, Liu PS, Steffek M, Lee J, Tam C, Helgason E, Murray JM, Kirkpatrick DS, Fairbrother WJ, Corn JE Proc Natl Acad Sci U S A. 2013 Jun 25. PMID:23801757 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D structures of ubiquitin

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