A solvent-exposed patch in chaperone-bound YopE is required for translocation by the type III secretion system.
Most effector proteins of bacterial type III secretion (T3S) systems require chaperone proteins for translocation into host cells. Such effectors are bound by chaperones in a conserved and characteristic manner, with the chaperone-binding (Cb) region of the effector wound around the chaperone in a highly extended conformation. This conformation has been suggested to serve as a translocation signal in promoting the association between the chaperone-effector complex and a bacterial component required for translocation. We sought to test a prediction of this model by identifying a potential association site for the Yersinia pseudotuberculosis chaperone-effector pair SycE-YopE. We identified a set of residues in the YopE Cb region that are required for translocation but are dispensable for expression, SycE binding, secretion into the extrabacterial milieu, and stability in mammalian cells. These residues form a solvent-exposed patch on the surface of the chaperone-bound Cb region, and thus their effect on translocation is consistent with the structure of the chaperone-bound Cb region serving as a signal for translocation.
Rodgers
Loren
L
Section of Molecular Biology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Mukerjea
Romila
R
Birtalan
Sara
S
Friedberg
Devorah
D
Ghosh
Partho
P
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D009154:Mutation; D011487:Protein Conformation; D021381:Protein Transport / Q000502:physiology*; D015011:Yersinia pseudotuberculosis / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D018832:Molecular Chaperones; C063239:yopE protein, Yersinia
Structure. 2004 Sep;12(9):1669-81
15341731
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):11998-2002
8618831
J Bacteriol. 2000 Sep;182(17):4811-21
10940022
Biochemistry. 2009 Dec 1;48(47):11158-60
19877667
Mol Cell. 2002 May;9(5):971-80
12049734
Mol Microbiol. 2002 Nov;46(4):1183-97
12421321
J Immunol. 2006 May 15;176(10):6093-102
16670318
EMBO Rep. 2004 May;5(5):477-83
15088068
Infect Immun. 1984 Jan;43(1):72-8
6317574
Mol Microbiol. 1998 Mar;27(5):953-65
9535085
J Mol Biol. 2007 Jan 26;365(4):1201-16
17174335
Infect Immun. 2001 May;69(5):3516-8
11292787
Mol Microbiol. 2002 Nov;46(3):769-79
12410834
Infect Immun. 1982 Aug;37(2):506-12
6749681
J Bacteriol. 1996 Dec;178(24):7227-33
8955406
EMBO J. 1996 Nov 1;15(21):5812-23
8918459
Mol Microbiol. 2007 Jul;65(2):386-400
17587230
J Bacteriol. 2008 May;190(9):3381-5
18310330
J Bacteriol. 2003 Dec;185(23):6747-55
14617638
Mol Microbiol. 1994 Nov;14(3):583-94
7885236
J Biol Chem. 2005 Sep 2;280(35):31149-55
16000312
Nat Rev Microbiol. 2006 Nov;4(11):811-25
17041629
Acta Crystallogr D Biol Crystallogr. 2004 Sep;60(Pt 9):1591-9
15333930
Microbiol Mol Biol Rev. 2004 Dec;68(4):771-95
15590783
Nat Struct Biol. 2001 Dec;8(12):1031-6
11685226
J Biol Chem. 2004 Jan 23;279(4):2747-53
14597627
Science. 1997 Nov 7;278(5340):1140-3
9353199
Mol Microbiol. 1995 May;16(4):635-47
7476159
Mol Microbiol. 2002 Jan;43(2):411-23
11985718
Infect Immun. 2009 Nov;77(11):4740-9
19687205
Nature. 2006 Nov 30;444(7119):567-73
17136086
Mol Microbiol. 1996 Jun;20(6):1261-71
8809777
Cell Microbiol. 2006 Jun;8(6):1020-33
16681842
J Biol Chem. 1999 Jul 30;274(31):22102-8
10419539
Proc Natl Acad Sci U S A. 1984 Nov;81(22):6929-33
6390428
Nature. 2001 Nov 1;414(6859):77-81
11689946
Mol Cell. 2006 Mar 3;21(5):653-64
16507363
Nature. 2005 Oct 6;437(7060):911-5
16208377
EMBO J. 2008 Jan 23;27(2):447-57
18188151
Mol Microbiol. 2002 Jan;43(1):51-9
11849536
Mol Microbiol. 1993 Apr;8(1):123-31
8497188
PLoS Pathog. 2008 Jan;4(1):e3
18193942
J Bacteriol. 2004 Aug;186(16):5486-95
15292151
EMBO J. 2006 Jul 12;25(13):3223-33
16794578
Mol Microbiol. 1998 Nov;30(4):865-82
10094634
J Mol Biol. 2005 Mar 4;346(4):1147-61
15701523
Protein Sci. 2005 Aug;14(8):1993-2002
16046625
Nat Struct Biol. 2001 Nov;8(11):974-8
11685245
Mol Microbiol. 1997 May;24(4):757-65
9194703
J Biol Chem. 2008 Jul 25;283(30):20857-63
18502763