7QBY

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

7QBY の概要

• エントリーDOI: 10.2210/pdb7qby/pdb
• NMR情報: BMRB: 34686
• 分子名称: Isoform B of DnaJ homolog subfamily B member 6 (1 entity in total)
• 機能のキーワード: hsp40 chaperone, anti-aggregation, chaperone
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6444.38

構造登録者

Karamanos, T.K.,Cawood, E.E. (登録日: 2021-11-21, 公開日: 2022-03-30, 最終更新日: 2024-06-19)

主引用文献

Cawood, E.E.,Clore, G.M.,Karamanos, T.K.
Microsecond Backbone Motions Modulate the Oligomerization of the DNAJB6 Chaperone.
Angew.Chem.Int.Ed.Engl., 61:e202116403-e202116403, 2022

PubMed Abstract: 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 β-stranded CTD but increases the population and rate of formation of a partially folded state. The results can be rationalized in terms of β-strand peptide plane flips that occur on a timescale of ≈100 μs 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.

PubMed: 35247211
DOI: 10.1002/anie.202116403

実験手法

SOLUTION NMR