Mutational analysis of the class IIa bacteriocin curvacin A and its orientation in target cell membranes.
To analyze the orientation in target cell membranes of the pediocin-like bacteriocin (antimicrobial peptide) curvacin A, 55 variants were generated by site-directed mutagenesis and their potencies against four different target cells determined. The result suggest that the somewhat hydrophilic short central helix (residues 19 to 24), along with the N-terminal beta-sheet-like structure (residues 1 to 16), inserts in the interface region of the target cell membrane, with Ala22 close to the hydrophobic core of the membrane. The following hinge region, with Gly28 as an important residue, may then form a turn wherein Gly28 becomes positioned near the border between the interface and the hydrophobic regions, thus permitting the longer and more-hydrophobic C-terminal helix (residues 29 to 41) to insert into the hydrophobic core of the membrane. This helix contains three glycine residues (G33, G37, and G40) that form a putative helix-helix-interacting GxxxGxxG motif. The replacement of any of these glycines with a larger residue was very detrimental, suggesting their possible involvement in helix-helix interactions with a membrane-embedded receptor protein.
Haugen
Helén Sophie
HS
Department of Molecular Biosciences, University of Oslo, Oslo, Norway. h.s.haugen@imbv.uio.no
Kristiansen
Per Eugen
PE
Fimland
Gunnar
G
Nissen-Meyer
Jon
J
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001430:Bacteriocins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry*; D004252:DNA Mutational Analysis; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C071456:sakacin A
Appl Environ Microbiol. 2006 Jul;72(7):4761-6
16820469
Int J Food Microbiol. 2003 Feb 25;81(1):29-40
12423916
Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2384-9
17284603
Trends Biochem Sci. 2000 Sep;25(9):429-34
10973056
Antimicrob Agents Chemother. 2004 Jul;48(7):2778-81
15215149
Microbiology (Reading). 2002 Jul;148(Pt 7):2019-2027
12101290
J Biol Chem. 2005 Mar 11;280(10):9243-50
15611086
Biochemistry. 2003 Oct 7;42(39):11417-26
14516192
Nat Rev Microbiol. 2005 Oct;3(10):777-88
16205711
Arch Biochem Biophys. 1992 May 15;295(1):5-12
1575516
Biochemistry. 1999 Nov 23;38(47):15438-47
10569926
Biochemistry. 2002 Jul 30;41(30):9508-15
12135373
Curr Opin Struct Biol. 2004 Aug;14(4):465-79
15313242
Biochemistry. 1997 Dec 9;36(49):15062-72
9398233
Appl Environ Microbiol. 2002 Aug;68(8):3830-40
12147478
Biochim Biophys Acta. 1998 Aug 14;1373(1):47-58
9733915
J Pept Sci. 2005 Nov;11(11):688-96
16059970
Appl Environ Microbiol. 2000 Dec;66(12):5213-20
11097892
Appl Environ Microbiol. 2002 Feb;68(2):952-6
11823243
Appl Environ Microbiol. 2005 Jan;71(1):554-7
15640235
Int J Food Microbiol. 2001 Dec 4;71(1):1-20
11764886
Arch Microbiol. 1997 Feb-Mar;167(2-3):67-77
9133328
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7617-21
17456596
Int J Food Microbiol. 2004 Dec 15;97(2):123-36
15541799
Antimicrob Agents Chemother. 2001 Mar;45(3):905-12
11181378
Methods Mol Biol. 1995;47:201-8
7550736
Microbiology (Reading). 2006 Jun;152(Pt 6):1649-1659
16735728
Biochim Biophys Acta. 2006 Jun;1764(6):1132-40
16762606
J Gen Microbiol. 1992 Dec;138(12):2715-20
1487735
Appl Environ Microbiol. 2002 Dec;68(12):6416-20
12450870
Appl Environ Microbiol. 2004 Aug;70(8):4672-80
15294801
Appl Environ Microbiol. 1996 Aug;62(8):2897-903
8702282
Appl Environ Microbiol. 1997 Nov;63(11):4321-30
9361419
J Biol Chem. 1996 Jun 14;271(24):14421-9
8662868
Int J Food Microbiol. 2001 Aug 15;68(1-2):93-104
11545225
Appl Environ Microbiol. 2001 Sep;67(9):4041-7
11526003
Appl Environ Microbiol. 1996 Dec;62(12):4410-6
8953713
Appl Environ Microbiol. 1992 Aug;58(8):2360-7
1514784
FEMS Microbiol Lett. 2001 Nov 27;205(1):49-55
11728715
J Bacteriol. 1996 Jun;178(12):3585-93
8655558
Appl Environ Microbiol. 1998 Dec;64(12):5057-60
9835610
J Bacteriol. 1991 Dec;173(23):7491-500
1840587
J Bacteriol. 1995 Apr;177(8):2125-37
7721704
J Appl Microbiol. 2001 Jul;91(1):131-8
11442722
J Med Chem. 2000 Nov 30;43(24):4579-81
11101349
Microbiology (Reading). 1998 Oct;144 ( Pt 10):2837-2844
9802025
Appl Environ Microbiol. 1996 May;62(5):1676-82
8633865
FEMS Microbiol Lett. 1998 Nov 1;168(1):137-43
9812374
Biochemistry. 2005 Dec 13;44(49):16149-57
16331975
J Biol Chem. 1994 Apr 22;269(16):12204-11
8163526
Appl Environ Microbiol. 1997 Dec;63(12):4770-7
9406395
Biochem Biophys Res Commun. 2002 Jul 26;295(4):826-7
12127968
Biosci Biotechnol Biochem. 2001 Feb;65(2):247-53
11302155
Appl Environ Microbiol. 2004 May;70(5):2647-52
15128514
Appl Environ Microbiol. 1987 Jul;53(7):1584-8
16347386
J Bacteriol. 2000 May;182(9):2643-8
10762272
J Bacteriol. 1992 Sep;174(17):5686-92
1512201