title: Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates.
abstract: Secretion systems require high-fidelity mechanisms to discriminate substrates among the vast cytoplasmic pool of proteins. Factors mediating substrate recognition by the type VI secretion system (T6SS) of Gram-negative bacteria, a widespread pathway that translocates effector proteins into target bacterial cells, have not been defined. We report that haemolysin coregulated protein (Hcp), a ring-shaped hexamer secreted by all characterized T6SSs, binds specifically to cognate effector molecules. Electron microscopy analysis of an Hcp-effector complex from Pseudomonas aeruginosa revealed the effector bound to the inner surface of Hcp. Further studies demonstrated that interaction with the Hcp pore is a general requirement for secretion of diverse effectors encompassing several enzymatic classes. Though previous models depict Hcp as a static conduit, our data indicate it is a chaperone and receptor of substrates. These unique functions of a secreted protein highlight fundamental differences between the export mechanism of T6 and other characterized secretory pathways.
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Julie M
authors: JM
authors: Silverman
authors: Danielle M
authors: DM
authors: Agnello
authors: Hongjin
authors: H
authors: Zheng
authors: Benjamin T
authors: BT
authors: Andrews
authors: Mo
authors: M
authors: Li
authors: Carlos E
authors: CE
authors: Catalano
authors: Tamir
authors: T
authors: Gonen
authors: Joseph D
authors: JD
authors: Mougous
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000502:physiology*; D006460:Hemolysin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009154:Mutation; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D006460:Hemolysin Proteins; D018832:Molecular Chaperones; D009113:Muramidase; D000581:Amidohydrolases; C019665:amidase
references: Microbiology (Reading). 2002 Jun;148(Pt 6):1604-1606
references: 12055281
references: Cell Host Microbe. 2012 May 17;11(5):538-49
references: 22607806
references: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3733-8
references: 18310321
references: Nat Biotechnol. 2005 Jul;23(7):873-8
references: 15980861
references: BMC Genomics. 2009 Aug 04;10:354
references: 19653904
references: Curr Opin Microbiol. 2013 Feb;16(1):52-8
references: 23290191
references: Structure. 2011 May 11;19(5):603-12
references: 21565695
references: Mol Microbiol. 2007 Dec;66(5):1192-206
references: 17986187
references: PLoS Pathog. 2012;8(4):e1002613
references: 22511866
references: Mol Microbiol. 2011 Dec;82(5):1277-90
references: 22017253
references: J Bacteriol. 2003 Apr;185(7):2330-7
references: 12644504
references: Nat Rev Microbiol. 2007 Nov;5(11):883-91
references: 17922044
references: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4067-8
references: 19276114
references: Science. 2006 Jun 9;312(5779):1526-30
references: 16763151
references: PLoS Pathog. 2012 Sep;8(9):e1002910
references: 23028312
references: Mol Microbiol. 2009 May;72(3):612-32
references: 19426209
references: Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2623-8
references: 23362380
references: J Mol Biol. 2012 Apr 6;417(4):351-61
references: 22310046
references: Annu Rev Microbiol. 2007;61:89-112
references: 17506669
references: Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):7032-7
references: 23572593
references: PLoS Pathog. 2011 Nov;7(11):e1002386
references: 22102820
references: Biochem J. 2013 Aug 15;454(1):59-68
references: 23730712
references: Science. 2012 Aug 17;337(6096):815
references: 22767897
references: Nat Rev Microbiol. 2006 Nov;4(11):811-25
references: 17041629
references: J Bacteriol. 2011 Dec;193(24):7001-2
references: 22123758
references: EMBO J. 2009 Feb 18;28(4):315-25
references: 19131969
references: Mol Cell. 2006 Jun 9;22(5):701-7
references: 16762842
references: Philos Trans R Soc Lond B Biol Sci. 2012 Apr 19;367(1592):1102-11
references: 22411981
references: Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18947-52
references: 19028873
references: PLoS Pathog. 2007 Dec;3(12):e188
references: 18069892
references: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14339-44
references: 14617778
references: PLoS One. 2013 Jul 05;8(7):e67647
references: 23861778
references: J Struct Funct Genomics. 2011 Mar;12(1):21-6
references: 21476004
references: Mol Microbiol. 2006 Oct;62(2):308-19
references: 17020575
references: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1528-33
references: 16432199
references: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15508-13
references: 17873062
references: Biol Proced Online. 2004;6:23-34
references: 15103397
references: J Biol Chem. 2011 Apr 8;286(14):12317-27
references: 21325275
references: Nat Rev Microbiol. 2009 Oct;7(10):703-14
references: 19756009
references: Microbiology (Reading). 2009 Feb;155(Pt 2):498-512
references: 19202098
references: Nature. 2000 Aug 31;406(6799):959-64
references: 10984043
references: Cell Host Microbe. 2010 Jan 21;7(1):25-37
references: 20114026
references: J Bacteriol. 2012 Sep;194(18):5101-9
references: 22821971
references: Nature. 2013 Apr 25;496(7446):508-12
references: 23552891
references: J Bacteriol. 2010 Jan;192(1):155-68
references: 19880608
references: J Biol Chem. 2013 Mar 15;288(11):7618-7625
references: 23341465
references: Nature. 2012 Feb 26;483(7388):182-6
references: 22367545
references: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4154-9
references: 19251641
references: Nature. 2001 Nov 1;414(6859):77-81
references: 11689946
references: J Bacteriol. 2008 Apr;190(8):2841-50
references: 18263727
references: Cell Microbiol. 2011 Aug;13(8):1286-301
references: 21729227
references: Nature. 2005 Oct 6;437(7060):911-5
references: 16208377
references: Plasmid. 2000 Jan;43(1):59-72
references: 10610820
references: J Struct Biol. 1996 Jan-Feb;116(1):190-9
references: 8742743
references: Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19804-9
references: 23150540
references: Mol Microbiol. 2010 May;76(4):815-21
references: 20444095
references: PLoS One. 2010 Sep 23;5(9):e12910
references: 20886112
references: Nature. 2011 Jul 20;475(7356):343-7
references: 21776080
references: J Biol Chem. 2013 Feb 22;288(8):5928-39
references: 23288853
references: Annu Rev Microbiol. 2012;66:453-72
references: 22746332
references: Cell Host Microbe. 2009 Jun 18;5(6):571-9
references: 19527884
references: Cell Rep. 2012 Jun 28;1(6):656-64
references: 22813741
references: Annu Rev Microbiol. 2005;59:451-85
references: 16153176