Mapping protein interactions in the active TOM-TIM23 supercomplex.


Journal

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

Informations de publication

Date de publication:
29 09 2021
Historique:
received: 22 12 2020
accepted: 19 08 2021
entrez: 30 9 2021
pubmed: 1 10 2021
medline: 24 10 2021
Statut: epublish

Résumé

Nuclear-encoded mitochondrial proteins destined for the matrix have to be transported across two membranes. The TOM and TIM23 complexes facilitate the transport of precursor proteins with N-terminal targeting signals into the matrix. During transport, precursors are recognized by the TIM23 complex in the inner membrane for handover from the TOM complex. However, we have little knowledge on the organization of the TOM-TIM23 transition zone and on how precursor transfer between the translocases occurs. Here, we have designed a precursor protein that is stalled during matrix transport in a TOM-TIM23-spanning manner and enables purification of the translocation intermediate. Combining chemical cross-linking with mass spectrometric analyses and structural modeling allows us to map the molecular environment of the intermembrane space interface of TOM and TIM23 as well as the import motor interactions with amino acid resolution. Our analyses provide a framework for understanding presequence handover and translocation during matrix protein transport.

Identifiants

pubmed: 34588454
doi: 10.1038/s41467-021-26016-1
pii: 10.1038/s41467-021-26016-1
pmc: PMC8481542
doi:

Substances chimiques

Cross-Linking Reagents 0
Membrane Transport Proteins 0
Mitochondrial Membrane Transport Proteins 0
Mitochondrial Precursor Protein Import Complex Proteins 0
Protein Precursors 0
Recombinant Proteins 0
Saccharomyces cerevisiae Proteins 0
TIM23 protein, S cerevisiae 0
TIM44 protein, S cerevisiae 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

5715

Informations de copyright

© 2021. The Author(s).

Références

J Mol Biol. 2011 Aug 19;411(3):513-9
pubmed: 21704637
Mol Cell Biol. 2014 Sep 15;34(18):3473-85
pubmed: 25002531
EMBO J. 1997 Sep 1;16(17):5408-19
pubmed: 9312000
Cell. 2002 Nov 15;111(4):519-28
pubmed: 12437925
EMBO J. 2003 Oct 1;22(19):4945-56
pubmed: 14517234
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11930-4
pubmed: 1465421
Protein Sci. 2010 Nov;19(11):2045-54
pubmed: 20718036
J Mol Biol. 2006 Jun 9;359(3):798-804
pubmed: 16647716
Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15179-83
pubmed: 21896724
Cell Res. 2021 Jul;31(7):821-824
pubmed: 33318647
EMBO J. 2013 Mar 20;32(6):886-98
pubmed: 23403928
Nature. 1994 Oct 27;371(6500):768-74
pubmed: 7935837
Mol Cell Proteomics. 2012 Mar;11(3):M111.014126
pubmed: 22286754
Proteins. 2009;77 Suppl 9:89-99
pubmed: 19701941
Cell. 2002 Nov 15;111(4):507-18
pubmed: 12437924
J Biol Chem. 2004 Oct 29;279(44):45701-7
pubmed: 15337763
Nature. 1999 Sep 30;401(6752):485-9
pubmed: 10519552
EMBO J. 2003 Oct 15;22(20):5370-81
pubmed: 14532110
Cell. 2005 Mar 25;120(6):817-29
pubmed: 15797382
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13839-44
pubmed: 14605210
Cell. 2000 May 12;101(4):401-12
pubmed: 10830167
EMBO J. 2006 Oct 4;25(19):4675-85
pubmed: 16977310
J Cell Biol. 1989 Oct;109(4 Pt 1):1421-8
pubmed: 2529262
Cell. 1995 Jan 13;80(1):127-37
pubmed: 7813008
Nat Struct Mol Biol. 2004 Mar;11(3):226-33
pubmed: 14981507
Mol Cell Biol. 1998 Nov;18(11):6515-24
pubmed: 9774667
J Mol Biol. 2012 Mar 16;417(1-2):1-12
pubmed: 22306468
Nat Cell Biol. 2007 Oct;9(10):1152-9
pubmed: 17828250
Mol Cell Biol. 2010 Jan;30(1):307-18
pubmed: 19884344
Cell. 1992 Mar 20;68(6):1163-75
pubmed: 1347713
Cell. 2000 Mar 3;100(5):551-60
pubmed: 10721992
Science. 2006 Jun 9;312(5779):1523-6
pubmed: 16763150
Cell. 2020 Mar 19;180(6):1130-1143.e20
pubmed: 32160528
J Biol Chem. 2011 Dec 23;286(51):43809-43815
pubmed: 21969381
Proteins. 2017 Mar;85(3):479-486
pubmed: 27667482
Nat Methods. 2015 Apr;12(4):361-365
pubmed: 25707030
Nat Struct Mol Biol. 2004 Mar;11(3):234-41
pubmed: 14981506
Cell. 1996 Oct 4;87(1):33-41
pubmed: 8858146
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12818-22
pubmed: 7809127
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
EMBO Rep. 2006 Dec;7(12):1233-8
pubmed: 17099692
EMBO J. 1995 Sep 1;14(17):4204-11
pubmed: 7556061
Cell. 1985 Nov;43(1):339-50
pubmed: 2866845
J Cell Biol. 2017 Jan 2;216(1):83-92
pubmed: 28011846
Nat Commun. 2014 Jul 10;5:4349
pubmed: 25008211
Mol Cell Biol. 1993 Dec;13(12):7364-71
pubmed: 8246957
J Mol Biol. 2020 May 1;432(10):3326-3337
pubmed: 32277989
J Mol Biol. 2000 Nov 3;303(4):479-88
pubmed: 11054285
Mol Biol Cell. 2008 Jan;19(1):159-70
pubmed: 17959826
Nat Struct Mol Biol. 2019 Dec;26(12):1158-1166
pubmed: 31740857
Elife. 2017 Apr 25;6:
pubmed: 28440746
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Methods Cell Biol. 2001;65:189-215
pubmed: 11381594
Nat Commun. 2019 Jul 30;10(1):3404
pubmed: 31363125
Methods Mol Biol. 2006;313:33-9
pubmed: 16118422
Science. 2015 Sep 25;349(6255):1544-8
pubmed: 26404837
J Cell Biol. 2003 Nov 24;163(4):707-13
pubmed: 14638855
Trends Cell Biol. 2015 May;25(5):265-75
pubmed: 25542066
Nat Methods. 2012 Sep;9(9):904-6
pubmed: 22772728
Nat Commun. 2018 Oct 2;9(1):4028
pubmed: 30279421
Nat Cell Biol. 2018 May;20(5):528-534
pubmed: 29662179
PLoS One. 2013 Sep 17;8(9):e73411
pubmed: 24069194
Bioinformatics. 2018 Oct 15;34(20):3461-3469
pubmed: 29718115
Mol Cell Biol. 2000 Aug;20(16):5879-87
pubmed: 10913171
Mol Cell Proteomics. 2015 Apr;14(4):1137-47
pubmed: 25648531
Annu Rev Biochem. 2007;76:723-49
pubmed: 17263664
Annu Rev Biochem. 2017 Jun 20;86:685-714
pubmed: 28301740
Mol Cell Biol. 1997 Nov;17(11):6574-84
pubmed: 9343421
J Cell Biol. 2011 Nov 14;195(4):643-56
pubmed: 22065641
Nature. 2019 Nov;575(7782):395-401
pubmed: 31600774
Cell Rep. 2020 Mar 3;30(9):3092-3104.e4
pubmed: 32130909
Nat Struct Biol. 2001 Dec;8(12):1074-82
pubmed: 11713477

Auteurs

Ridhima Gomkale (R)

Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.

Andreas Linden (A)

Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen, Germany.

Piotr Neumann (P)

Department for Molecular Structural Biology, Georg-August-Universität Göttingen, Göttingen, Germany.

Alexander Benjamin Schendzielorz (AB)

Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.

Stefan Stoldt (S)

Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Clinic of Neurology, University Medical Center Göttingen, Göttingen, Germany.

Olexandr Dybkov (O)

Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen, Germany.

Markus Kilisch (M)

Department of Molecular Biology, University Medical Center Göttingen, Göttingen, Germany.

Christian Schulz (C)

Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.

Luis Daniel Cruz-Zaragoza (LD)

Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.

Blanche Schwappach (B)

Department of Molecular Biology, University Medical Center Göttingen, Göttingen, Germany.

Ralf Ficner (R)

Department for Molecular Structural Biology, Georg-August-Universität Göttingen, Göttingen, Germany.
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany.

Stefan Jakobs (S)

Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Clinic of Neurology, University Medical Center Göttingen, Göttingen, Germany.
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany.

Henning Urlaub (H)

Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen, Germany.

Peter Rehling (P)

Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany. peter.rehling@medizin.uni-goettingen.de.
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany. peter.rehling@medizin.uni-goettingen.de.
Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. peter.rehling@medizin.uni-goettingen.de.

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Classifications MeSH