A nexus of intrinsic dynamics underlies translocase priming.

Bacillus subtilis / enzymology Bacterial Proteins / chemistry Catalytic Domain Hydrogen Bonding Models, Molecular Molecular Dynamics Simulation Multiprotein Complexes / chemistry Protein Binding Protein Conformation Protein Domains SEC Translocation Channels / metabolism SecA Proteins / chemistry
HDX-MS MD simulation SecA SecYEG channel graph analysis intrinsic dynamics protein secretion signal peptide smFRET translocase

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
05 08 2021
Historique:
received: 29 01 2021
revised: 06 03 2021
accepted: 25 03 2021
pubmed: 15 4 2021
medline: 12 1 2022
entrez: 14 4 2021
Statut: ppublish

Résumé

The cytoplasmic ATPase SecA and the membrane-embedded SecYEG channel assemble to form the Sec translocase. How this interaction primes and catalytically activates the translocase remains unclear. We show that priming exploits a nexus of intrinsic dynamics in SecA. Using atomistic simulations, smFRET, and HDX-MS, we reveal multiple dynamic islands that cross-talk with domain and quaternary motions. These dynamic elements are functionally important and conserved. Central to the nexus is a slender stem through which rotation of the preprotein clamp of SecA is biased by ATPase domain motions between open and closed clamping states. An H-bonded framework covering most of SecA enables multi-tier dynamics and conformational alterations with minimal energy input. As a result, cognate ligands select preexisting conformations and alter local dynamics to regulate catalytic activity and clamp motions. These events prime the translocase for high-affinity reception of non-folded preprotein clients. Dynamics nexuses are likely universal and essential in multi-liganded proteins.

Identifiants

DOI: 10.1016/j.str.2021.03.015 PMID: 33852897
pubmed: 33852897
pii: S0969-2126(21)00113-1
doi: 10.1016/j.str.2021.03.015
pii:
doi:

Substances chimiques

Bacterial Proteins 0
Multiprotein Complexes 0
SEC Translocation Channels 0
SecA Proteins EC 7.4.2.4

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

846-858.e7

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare they have no competing financial interests or other conflicts of interest.

Auteurs

Srinath Krishnamurthy (S)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium.

Nikolaos Eleftheriadis (N)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium.

Konstantina Karathanou (K)

Freie Universität Berlin, Department of Physics, Theoretical Molecular Biophysics Group, Arnimallee 14, 14195 Berlin, Germany.

Jochem H Smit (JH)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium.

Athina G Portaliou (AG)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium.

Katerina E Chatzi (KE)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium.

Spyridoula Karamanou (S)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium.

Ana-Nicoleta Bondar (AN)

Freie Universität Berlin, Department of Physics, Theoretical Molecular Biophysics Group, Arnimallee 14, 14195 Berlin, Germany.

Giorgos Gouridis (G)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium; Molecular Microscopy Research Group, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, the Netherlands; Structural Biology Division, Institute of Molecular Biology and Biotechnology (IMBB-FORTH), Nikolaou Plastira 100, Heraklion-Crete, Greece. Electronic address: g.gouridis@imbb.forth.gr.

Anastassios Economou (A)

KU Leuven, University of Leuven, Rega Institute, Department of Microbiology and Immunology, 3000 Leuven, Belgium. Electronic address: tassos.economou@kuleuven.be.

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Classifications MeSH

questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets sporulés à Gram positif › Bacillaceae › Bacillus › Bacillus subtilis › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines bactériennes › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Domaine catalytique › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Phénomènes chimiques › Liaison hydrogène › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de dynamique moléculaire › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Structures macromoléculaires › Complexes multiprotéiques › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structure tertiaire des protéines › Domaines protéiques › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux de translocation SEC › A nexus of intrinsic dynamics underlies...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Acid anhydride hydrolases › Adenosine triphosphatases › Protéines SecA › A nexus of intrinsic dynamics underlies...