期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 430, 期 18, 页码 3157-3169出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2018.07.014
关键词
Yersinia; NMR spectroscopy; protein complex; binding mechanism
资金
- Swedish Research Council [2013-5954]
- Knut and Alice Wallenberg Foundation
- Carl Tryggers Foundation [CTS 15:210]
- Kempe foundation
- Helmholtz Association through the Impuls-und Vernetzungsfond
- Human Frontier Science Program [RGP0017/2012]
- BBSRC [BB/J014346/1] Funding Source: UKRI
Bacterial virulence is typically initiated by translocation of effector or toxic proteins across host cell membranes. A class of gram-negative pathogenic bacteria including Yersinia pseudotuberculosis and Yersinia pestis accomplishes this objective with a protein assembly called the type III secretion system. Yersinia effector proteins (Yop) are presented to the translocation apparatus through formation of specific complexes with their cognate chaperones (Syc). In the complexes where the structure is available, the Yops are extended and wrap around their cognate chaperone. This structural architecture enables secretion of the Yop from the bacterium in early stages of translocation. It has been shown previously that the chaperone-binding domain of YopE is disordered in its isolation but becomes substantially more ordered in its wrap-around complex with its chaperone SycE. Here, by means of NMR spectroscopy, small-angle X-ray scattering and molecular modeling, we demonstrate that while the free chaperone-binding domain of YopH (YopH(CBD)) adopts a fully ordered and globular fold, it populates an elongated, wrap-around conformation when it engages in a specific complex with its chaperone SycH(2). Hence, in contrast to YopE that is unstructured in its free state, YopH transits from a globular free state to an elongated chaperone-bound state. We demonstrate that a sparsely populated YopH(CBD) state has an elevated affinity for SycH(2) and represents an intermediate in the formation of the protein complex. Our results suggest that Yersinia has evolved a binding mechanism where SycH(2) passively stimulates an elongated YopH conformation that is presented to the type III secretion system in a secretion-competent conformation. (C) 2018 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据