Protein quality control and regulated proteolysis in the genome-reduced organism Mycoplasma pneumoniae.
Amino Acid Sequence
Bacterial Proteins
/ chemistry
Gene Expression Regulation, Bacterial
Genome, Bacterial
Models, Biological
Mutation
/ genetics
Mycoplasma pneumoniae
/ enzymology
Peptide Hydrolases
/ metabolism
Phenotype
Protein Folding
Proteolysis
Quality Control
Reproducibility of Results
Substrate Specificity
Transcription, Genetic
ATP-dependent protease
mycoplasma
protein degradation
proteomic approach
regulated proteolysis
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
19
02
2020
revised:
04
11
2020
accepted:
08
11
2020
entrez:
15
12
2020
pubmed:
16
12
2020
medline:
27
8
2021
Statut:
ppublish
Résumé
Protein degradation is a crucial cellular process in all-living systems. Here, using Mycoplasma pneumoniae as a model organism, we defined the minimal protein degradation machinery required to maintain proteome homeostasis. Then, we conditionally depleted the two essential ATP-dependent proteases. Whereas depletion of Lon results in increased protein aggregation and decreased heat tolerance, FtsH depletion induces cell membrane damage, suggesting a role in quality control of membrane proteins. An integrative comparative study combining shotgun proteomics and RNA-seq revealed 62 and 34 candidate substrates, respectively. Cellular localization of substrates and epistasis studies supports separate functions for Lon and FtsH. Protein half-life measurements also suggest a role for Lon-modulated protein decay. Lon plays a key role in protein quality control, degrading misfolded proteins and those not assembled into functional complexes. We propose that regulating complex assembly and degradation of isolated proteins is a mechanism that coordinates important cellular processes like cell division. Finally, by considering the entire set of proteases and chaperones, we provide a fully integrated view of how a minimal cell regulates protein folding and degradation.
Identifiants
pubmed: 33320415
doi: 10.15252/msb.20209530
pmc: PMC7737663
doi:
Substances chimiques
Bacterial Proteins
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e9530Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Cold Spring Harb Perspect Biol. 2011 Apr 01;3(4):
pubmed: 21441580
Nucleic Acids Res. 2016 Jan 4;44(D1):D343-50
pubmed: 26527717
Res Microbiol. 2006 Oct;157(8):701-13
pubmed: 16854568
Nucleic Acids Res. 2016 Feb 18;44(3):1192-202
pubmed: 26773059
Mol Microbiol. 2009 Apr;72(2):506-17
pubmed: 19317833
J Proteome Res. 2013 Feb 1;12(2):547-58
pubmed: 23253041
Nature. 2016 Nov 3;539(7627):48-53
pubmed: 27749819
Antimicrob Agents Chemother. 2012 Jun;56(6):2879-87
pubmed: 22450976
DNA Res. 2018 Aug 1;25(4):383-393
pubmed: 29659762
Microbiology (Reading). 2006 Feb;152(Pt 2):519-527
pubmed: 16436439
DNA Res. 2016 Jun;23(3):263-70
pubmed: 27084897
Bioinformatics. 2019 Oct 15;35(20):4168-4169
pubmed: 30874800
Appl Microbiol Biotechnol. 2015 Jun;99(12):5151-62
pubmed: 25750031
Mol Microbiol. 2005 Mar;55(6):1722-34
pubmed: 15752196
Nucleic Acids Res. 2016 Dec 15;44(22):11033
pubmed: 27683222
Mol Microbiol. 2013 Jun;88(6):1083-92
pubmed: 23647068
J Bacteriol. 2002 Sep;184(17):4775-82
pubmed: 12169602
Annu Rev Biochem. 2011;80:587-612
pubmed: 21469952
Microbiology (Reading). 2004 Feb;150(Pt 2):437-446
pubmed: 14766922
Infect Immun. 2013 Oct;81(10):3742-9
pubmed: 23897620
Science. 2009 Nov 27;326(5957):1235-40
pubmed: 19965468
Electrophoresis. 1999 Dec;20(18):3551-67
pubmed: 10612281
Mol Microbiol. 2012 Aug;85(4):669-83
pubmed: 22686427
Mol Syst Biol. 2011 Jul 19;7:511
pubmed: 21772259
Biostatistics. 2008 Apr;9(2):321-32
pubmed: 17728317
Science. 2009 Nov 27;326(5957):1268-71
pubmed: 19965477
BMC Bioinformatics. 2016 May 10;17:208
pubmed: 27161244
J Proteome Res. 2015 Jun 5;14(6):2457-65
pubmed: 25827922
Nat Commun. 2017 Mar 08;8:14665
pubmed: 28272414
Curr Opin Microbiol. 2017 Apr;36:118-127
pubmed: 28458096
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W382-8
pubmed: 15980494
Mol Syst Biol. 2020 May;16(5):e9208
pubmed: 32449593
FEBS J. 2005 Jun;272(11):2892-900
pubmed: 15943820
EMBO J. 1997 Aug 1;16(15):4579-90
pubmed: 9303302
Proteomics. 2018 Jul;18(13):e1800080
pubmed: 29710379
Mol Microbiol. 2004 Jun;52(6):1757-67
pubmed: 15186423
Genes Dev. 2008 Aug 15;22(16):2267-77
pubmed: 18708584
ACS Synth Biol. 2020 Jul 17;9(7):1693-1704
pubmed: 32502342
Trends Biochem Sci. 2019 Jun;44(6):528-545
pubmed: 30773324
Proc Int Conf Intell Syst Mol Biol. 1998;6:175-82
pubmed: 9783223
Cell Rep. 2014 Dec 11;9(5):1959-1965
pubmed: 25466257
Res Microbiol. 2009 Nov;160(9):645-51
pubmed: 19772918
Nucleic Acids Res. 1996 Nov 15;24(22):4420-49
pubmed: 8948633
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4532-6
pubmed: 7753838
Science. 1996 Feb 16;271(5251):990-3
pubmed: 8584937
Microbiology (Reading). 2001 Apr;147(Pt 4):1045-1057
pubmed: 11283300
Nat Methods. 2020 Mar;17(3):261-272
pubmed: 32015543
Proteomics. 2016 Dec;16(24):3161-3172
pubmed: 27766750
Mol Microbiol. 2014 Oct;94(2):290-306
pubmed: 25138908
J Biol Chem. 2008 Aug 22;283(34):22918-29
pubmed: 18550539
Mol Cell Proteomics. 2019 Sep;18(9):1880-1892
pubmed: 31235637
Biopolymers. 2016 Aug;105(8):505-17
pubmed: 26971705
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Bioinformatics. 2007 Nov 1;23(21):2881-7
pubmed: 17881408
J Bacteriol. 2008 Sep;190(18):6070-5
pubmed: 18621895
Mol Microbiol. 1999 Feb;31(3):833-44
pubmed: 10048027
Mol Microbiol. 1997 Mar;23(5):921-33
pubmed: 9076729
Nat Biotechnol. 2019 Apr;37(4):420-423
pubmed: 30778233
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
PLoS Pathog. 2015 Dec 03;11(12):e1005299
pubmed: 26633540
Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10291-6
pubmed: 8816793
Trends Cell Biol. 2007 Apr;17(4):165-72
pubmed: 17306546
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14244-9
pubmed: 11724963
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Science. 2000 Sep 29;289(5488):2354-6
pubmed: 11009422
Annu Rev Biochem. 2018 Jun 20;87:677-696
pubmed: 29648875
J Bacteriol. 1999 Dec;181(24):7531-44
pubmed: 10601211
Mol Microbiol. 2006 Jun;60(6):1490-508
pubmed: 16796683
Biol Chem. 2017 May 1;398(5-6):625-635
pubmed: 28085670
Mol Cell. 2003 Mar;11(3):671-83
pubmed: 12667450
Microbiol Mol Biol Rev. 2013 Mar;77(1):53-72
pubmed: 23471617
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34
pubmed: 25199790
PLoS One. 2018 Jan 11;13(1):e0189209
pubmed: 29324744
EMBO J. 1997 Apr 1;16(7):1501-7
pubmed: 9130695
EMBO Rep. 2000 Jul;1(1):47-52
pubmed: 11256624
FEMS Microbiol Rev. 2017 Aug 1;41(Supp_1):S3-S15
pubmed: 28830092
Nat Methods. 2009 May;6(5):359-62
pubmed: 19377485
J Neurosci Methods. 2000 Jul 31;100(1-2):157-63
pubmed: 11040379
Cell. 1999 Dec 23;99(7):757-68
pubmed: 10619429
FEMS Microbiol Lett. 2001 Apr 20;198(1):1-7
pubmed: 11325545
Nature. 2006 Feb 9;439(7077):753-6
pubmed: 16467841
Mol Syst Biol. 2019 Feb 22;15(2):e8290
pubmed: 30796087
Mol Biosyst. 2013 Jul;9(7):1743-55
pubmed: 23598864
Nature. 2011 May 19;473(7347):337-42
pubmed: 21593866
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Biochim Biophys Acta. 2008 Oct;1783(10):1815-25
pubmed: 18619498
Genes Cells. 2013 Apr;18(4):266-77
pubmed: 23461534
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Mol Syst Biol. 2015 Jan 21;11(1):780
pubmed: 25609650
Cell Syst. 2019 Aug 28;9(2):143-158.e13
pubmed: 31445891
Mol Microbiol. 2014 Sep;93(5):853-66
pubmed: 24989075
Science. 2009 Nov 27;326(5957):1263-8
pubmed: 19965476
Mol Cell Proteomics. 2002 Aug;1(8):579-91
pubmed: 12376573
J Bacteriol. 2011 Apr;193(8):1911-8
pubmed: 21317324
Mol Biol Evol. 2017 Aug 1;34(8):2115-2122
pubmed: 28460117
Biochem Biophys Res Commun. 2000 Apr 13;270(2):387-92
pubmed: 10753635
Nucleic Acids Res. 2016 Jan 4;44(D1):D286-93
pubmed: 26582926
EMBO J. 2009 Jun 17;28(12):1732-44
pubmed: 19440203