Structural Variability of EspG Chaperones from Mycobacterial ESX-1, ESX-3, and ESX-5 Type VII Secretion Systems.

Autor: Tuukkanen AT; European Molecular Biology Laboratory, Hamburg Unit, Hamburg 22607, Germany., Freire D; European Molecular Biology Laboratory, Hamburg Unit, Hamburg 22607, Germany., Chan S; UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Arbing MA; UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Reed RW; Department of Molecular & Cellular Biochemistry, and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA., Evans TJ; Department of Molecular & Cellular Biochemistry, and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA., Zenkeviciutė G; European Molecular Biology Laboratory, Hamburg Unit, Hamburg 22607, Germany., Kim J; UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Kahng S; UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Sawaya MR; UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Chaton CT; Department of Molecular & Cellular Biochemistry, and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA., Wilmanns M; European Molecular Biology Laboratory, Hamburg Unit, Hamburg 22607, Germany., Eisenberg D; UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Parret AHA; European Molecular Biology Laboratory, Hamburg Unit, Hamburg 22607, Germany. Electronic address: parret@embl-hamburg.de., Korotkov KV; Department of Molecular & Cellular Biochemistry, and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: kkorotkov@uky.edu.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2019 Jan 18; Vol. 431 (2), pp. 289-307. Date of Electronic Publication: 2018 Nov 10.
DOI: 10.1016/j.jmb.2018.11.003
Abstrakt: Type VII secretion systems (ESX) are responsible for transport of multiple proteins in mycobacteria. How different ESX systems achieve specific secretion of cognate substrates remains elusive. In the ESX systems, the cytoplasmic chaperone EspG forms complexes with heterodimeric PE-PPE substrates that are secreted from the cells or remain associated with the cell surface. Here we report the crystal structure of the EspG 1 chaperone from the ESX-1 system determined using a fusion strategy with T4 lysozyme. EspG 1 adopts a quasi 2-fold symmetric structure that consists of a central β-sheet and two α-helical bundles. In addition, we describe the structures of EspG 3 chaperones from four different crystal forms. Alternate conformations of the putative PE-PPE binding site are revealed by comparison of the available EspG 3 structures. Analysis of EspG 1 , EspG 3 , and EspG 5 chaperones using small-angle X-ray scattering reveals that EspG 1 and EspG 3 chaperones form dimers in solution, which we observed in several of our crystal forms. Finally, we propose a model of the ESX-3 specific EspG 3 -PE5-PPE4 complex based on the small-angle X-ray scattering analysis.
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Databáze: MEDLINE