Perforin-2 clockwise hand-over-hand pre-pore to pore transition mechanism.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 08 2022
Historique:
received: 23 03 2022
accepted: 16 08 2022
entrez: 26 8 2022
pubmed: 27 8 2022
medline: 31 8 2022
Statut: epublish

Résumé

Perforin-2 (PFN2, MPEG1) is a pore-forming protein that acts as a first line of defense in the mammalian immune system, rapidly killing engulfed microbes within the phagolysosome in macrophages. PFN2 self-assembles into hexadecameric pre-pore rings that transition upon acidification into pores damaging target cell membranes. Here, using high-speed atomic force microscopy (HS-AFM) imaging and line-scanning and molecular dynamics simulation, we elucidate PFN2 pre-pore to pore transition pathways and dynamics. Upon acidification, the pre-pore rings (pre-pore-I) display frequent, 1.8 s

Identifiants

pubmed: 36028507
doi: 10.1038/s41467-022-32757-4
pii: 10.1038/s41467-022-32757-4
pmc: PMC9418332
doi:

Substances chimiques

Pore Forming Cytotoxic Proteins 0
Perforin 126465-35-8

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5039

Subventions

Organisme : NCCIH NIH HHS
ID : DP1 AT010874
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS110790
Pays : United States
Organisme : Wellcome Trust
ID : 090532/Z/09/Z
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Fang Jiao (F)

Department of Anesthesiology, Weill Cornell Medicine, New York City, NY, USA. fang.jiao@iphy.ac.cn.
Department of Physiology and Biophysics, Weill Cornell Medicine, New York City, NY, USA. fang.jiao@iphy.ac.cn.
Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China. fang.jiao@iphy.ac.cn.

François Dehez (F)

Laboratoire International Associé, Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche no 7019, Université de Lorraine, Vandœuvre-lès-Nancy cedex, France.

Tao Ni (T)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.

Xiulian Yu (X)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
Calleva Research Centre for Evolution and Human Sciences, Magdalen College, University of Oxford, Oxford, UK.

Jeremy S Dittman (JS)

Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA.

Robert Gilbert (R)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
Calleva Research Centre for Evolution and Human Sciences, Magdalen College, University of Oxford, Oxford, UK.

Christophe Chipot (C)

Laboratoire International Associé, Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche no 7019, Université de Lorraine, Vandœuvre-lès-Nancy cedex, France.
Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Simon Scheuring (S)

Department of Anesthesiology, Weill Cornell Medicine, New York City, NY, USA. sis2019@med.cornell.edu.
Department of Physiology and Biophysics, Weill Cornell Medicine, New York City, NY, USA. sis2019@med.cornell.edu.
Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, New York, USA. sis2019@med.cornell.edu.

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