Unknown

Dataset Information

0

Structural basis and mechanism of the unfolding-induced activation of HdeA, a bacterial acid response chaperone.


ABSTRACT: The role of protein structural disorder in biological functions has gained increasing attention in the past decade. The bacterial acid-resistant chaperone HdeA belongs to a group of "conditionally disordered" proteins, because it is inactive in its well-structured state and becomes activated via an order-to-disorder transition under acid stress. However, the mechanism for unfolding-induced activation remains unclear because of a lack of experimental information on the unfolded state conformation and the chaperone-client interactions. Herein, we used advanced solution NMR methods to characterize the activated-state conformation of HdeA under acidic conditions and identify its client-binding sites. We observed that the structure of activated HdeA becomes largely disordered and exposes two hydrophobic patches essential for client interactions. Furthermore, using the pH-dependent chemical exchange saturation transfer (CEST) NMR method, we identified three acid-sensitive regions that act as structural locks in regulating the exposure of the two client-binding sites during the activation process, revealing a multistep activation mechanism of HdeA's chaperone function at the atomic level. Our results highlight the role of intrinsic protein disorder in chaperone function and the self-inhibitory role of ordered structures under nonstress conditions, offering new insights for improving our understanding of protein structure-function paradigms.

SUBMITTER: Yu XC 

PROVIDER: S-EPMC6398119 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5738273 | biostudies-literature
| S-EPMC3926742 | biostudies-literature
| S-EPMC8221390 | biostudies-literature
| S-EPMC3808462 | biostudies-literature
| S-EPMC3619340 | biostudies-literature
| S-EPMC3915903 | biostudies-literature
| S-EPMC2867010 | biostudies-literature
| S-EPMC5915598 | biostudies-literature
| S-EPMC5975942 | biostudies-literature
| S-EPMC6755796 | biostudies-literature