7qby

Refined structure of the T193A mutant in the C-terminal domain of DNAJB6b

spinqualitylabelsall models 7qby Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 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 DNAJB6 is a prime example of an anti-aggregation chaperone that functions as an oligomer. DNAJB6 oligomers are dynamic and subunit exchange is critical for inhibiting client protein aggregation. The T193A mutation in the C-terminal domain (CTD) of DNAJB6 reduces both chaperone self-oligomerization and anti-aggregation of client proteins, and has recently been linked to Parkinson's disease. Here, we show by NMR, including relaxation-based methods, that the T193A mutation has minimal effects on the structure of the beta-stranded CTD but increases the population and rate of formation of a partially folded state. The results can be rationalized in terms of beta-strand peptide plane flips that occur on a timescale of approximately 100 mus and lead to global changes in the overall pleat/flatness of the CTD, thereby altering its ability to oligomerize. These findings help forge a link between chaperone dynamics, oligomerization and anti-aggregation activity which may possibly lead to new therapeutic avenues tuned to target specific substrates. Microsecond Backbone Motions Modulate the Oligomerization of the DNAJB6 Chaperone.,Cawood EE, Clore GM, Karamanos TK Angew Chem Int Ed Engl. 2022 Mar 5:e202116403. doi: 10.1002/anie.202116403. PMID:35247211 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DnaJ homolog 3D structures

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