Inherent Minor Conformer of Bordetella Effector BteA Directs Chaperone-Mediated Unfolding

Adi Yahalom, Hadassa Shaked, Sharon Ruthstein, Jordan H. Chill

Research output: Contribution to journalArticlepeer-review

Abstract

The pathogen Bordetella pertussis uses a type-3 secretion system (T3SS) to inject its cytotoxic effector BteA into the host cell via a designated needle structure. Prior to injection BteA is bound to its cognate chaperone BtcA presumed to assist in effector unfolding en route to needle passage. We utilized NMR and EPR spectroscopy to uncover the molecular mechanism of BtcA-mediated unfolding of BteA. BtcA induces a global structural change in the effector, which adopts a more extended and partially unfolded conformation. EPR distance measurements further show that the structured helical-bundle form of free BteA exists in conformational equilibrium with a lowly populated minor species. The nature of this equilibrium was probed using NMR relaxation dispersion experiments. At 283 K structural effects are most pronounced for a contiguous surface spanning the A- and B-helices of BteA, extending at 303 K to a second surface including the D- and E-helices. Residues perturbed in the minor conformation coincide with those exhibiting a BtcA-induced increase in flexibility, identifying this conformation as the BtcA-bound form of the effector. Our findings hint at a conformational-selectivity mechanism for the chaperone interaction with the effector, a paradigm that may be common to effector-chaperones secretion complexes in this family of pathogens.

Original languageEnglish
Pages (from-to)11553-11557
Number of pages5
JournalJournal of the American Chemical Society
Volume144
Issue number26
DOIs
StatePublished - 6 Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 American Chemical Society.

Funding

We thank K. Keinan-Adamsky, H. Gottlieb, and Y. Tabakman for spectrometer support, G. Davidov and R. Zarivach for reagents and assistance for expression of BteA and BtcA, and M. Drori for her supporting role in analysis of relaxation dispersion data. This work was supported by the Israel Science Foundation (Grant 964/19).

FundersFunder number
Israel Science Foundation964/19

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