7QBY
Refined structure of the T193A mutant in the C-terminal domain of DNAJB6b
Summary for 7QBY
| Entry DOI | 10.2210/pdb7qby/pdb |
| NMR Information | BMRB: 34686 |
| Descriptor | Isoform B of DnaJ homolog subfamily B member 6 (1 entity in total) |
| Functional Keywords | hsp40 chaperone, anti-aggregation, chaperone |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 6444.38 |
| Authors | Karamanos, T.K.,Cawood, E.E. (deposition date: 2021-11-21, release date: 2022-03-30, Last modification date: 2024-06-19) |
| Primary citation | 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 Cited by 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: 35247211DOI: 10.1002/anie.202116403 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
