Membrane-Induced Structure of Scyliorhinin I: A Dual NK1/NK2 Agonist.
Scyliorhinin I, a linear decapeptide, is the only known tachykinin that shows high affinity for both NK-1 and NK-2 binding sites and low affinity for NK-3 binding sites. As a first step to understand the structure-activity relationship, we report the membrane-induced structure of scyliorhinin I with the aid of circular dichroism and 2D-(1)H NMR spectroscopy. Sequence specific resonance assignments of protons have been made from correlation spectroscopy (TOCSY, DQF-COSY) and NOESY spectroscopy. The interproton distance constraints and dihedral angle constraints have been utilized to generate a family of structures using DYANA. The superimposition of 20 final structures has been reported with backbone pairwise root mean-square deviation of 0.38 +/- 0.19 A. The results show that scyliorhinin I exists in a random coil state in aqueous environments, whereas helical conformation is induced toward the C-terminal region of the peptide (D4-M10) in the presence of dodecyl phosphocholine micelles. Analysis of NMR data is suggestive of the presence of a 3(10)-helix that is in equilibrium with an alpha-helix in this region from residue 4 to 10. An extended highly flexible N-terminus of scyliorhinin I displays some degree of order and a possible turn structure. Observed conformational features have been compared with respect to that of substance P and neurokinin A, which are endogenous agonists of NK-1 and NK-2 receptors, respectively.
Dike
Anjali
A
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Cowsik
Sudha M
SM
D000818:Animals; D002118:Calcium / Q000737:chemistry; D002942:Circular Dichroism; D007477:Ions; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D010767:Phosphorylcholine / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D018040:Receptors, Neurokinin-1 / Q000819:agonists*; D018041:Receptors, Neurokinin-2 / Q000819:agonists*; D013329:Structure-Activity Relationship; D015320:Tachykinins / Q000737:chemistry*
D007477:Ions; D008024:Ligands; D008055:Lipids; D008823:Micelles; D010455:Peptides; D011522:Protons; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C048918:scyliorhinin I; D010767:Phosphorylcholine; D002118:Calcium
Life Sci. 1988;42(26):2701-8
2838713
Biochim Biophys Acta. 1988 Jun 13;954(3):287-302
2453217
Biochemistry. 1989 Mar 21;28(6):2490-6
2471549
J Mol Biol. 1990 Oct 20;215(4):607-22
2231722
Annu Rev Neurosci. 1991;14:123-36
1851606
Biochem Cell Biol. 1991 Feb-Mar;69(2-3):93-5
1674422
Annu Rev Biophys Biophys Chem. 1991;20:519-38
1867725
Proteins. 1991;10(2):130-9
1896426
Neuropeptides. 1991 Aug;19(4):259-70
1717877
Biochemistry. 1992 Feb 18;31(6):1647-51
1737021
Biochemistry. 1992 Mar 24;31(11):2897-904
1372515
Biochim Biophys Acta. 1992 Apr 13;1105(2):319-27
1586668
Mol Pharmacol. 1992 Jun;41(6):1096-9
1377326
Biopolymers. 1992 Dec;32(12):1765-73
1282041
J Pharmacol Exp Ther. 1993 Jan;264(1):17-21
8380857
Biochemistry. 1993 Feb 16;32(6):1632-40
8431443
Biochemistry. 1993 May 11;32(18):4881-94
8387821
Biochemistry. 1993 Jul 27;32(29):7406-12
8393341
Eur J Pharmacol. 1993 Dec 7;250(2):311-6
7509285
Biochemistry. 1994 Jun 7;33(22):6802-11
8204614
J Mol Biol. 1994 Sep 30;242(4):497-507
7932706
Biochemistry. 1995 Mar 28;34(12):3873-7
7696249
Biochemistry. 1996 Apr 9;35(14):4365-74
8605185
Int J Biochem Cell Biol. 1996 Jul;28(7):721-38
8925404
Biopolymers. 1996;40(5):445-64
9062068
J Biomol Struct Dyn. 1997 Aug;15(1):27-36
9283976
Nat Struct Biol. 1997 Oct;4 Suppl:845-8
9377156
J Mol Biol. 1997 Oct 17;273(1):283-98
9367762
J Med Chem. 1998 Apr 23;41(9):1497-506
9554882
J Pept Res. 1998 Sep;52(3):185-94
9774231
Protein Sci. 1999 Feb;8(2):370-80
10048330
J Struct Biol. 2004 Dec;148(3):315-25
15522780
J Mol Biol. 2003 Feb 7;326(1):273-91
12547209
J Pept Sci. 2000 Feb;6(2):57-83
10718128
J Pept Res. 2000 Sep;56(3):132-46
11007270
J Biomol Struct Dyn. 2001 Feb;18(4):611-21, 623-5
11245256
Neuropeptides. 2001 Feb;35(1):24-31
11346307
Am J Gastroenterol. 2001 Nov;96(11):3117-21
11721758
Biochemistry. 2002 Jun 4;41(22):6911-9
12033923
Pharmacol Rev. 2002 Jun;54(2):285-322
12037144
Biophys J. 2003 Jan;84(1):655-64
12524318
Neuropeptides. 2003 Feb;37(1):30-5
12637033
Biophys J. 2003 Dec;85(6):4002-11
14645089
J Biomol Struct Dyn. 2004 Oct;22(2):137-48
15317475
Biochem Biophys Res Commun. 1983 Jun 29;113(3):967-74
6307308
Pharmacol Rev. 1983 Jun;35(2):85-141
6196797
J Mol Biol. 1984 Dec 15;180(3):741-51
6084720
FEBS Lett. 1986 May 5;200(1):111-6
2422058
EMBO J. 1987 Aug;6(8):2255-9
2822384
Nature. 1987 Oct 29-Nov 4;329(6142):766-7
2823145
Nature. 1987 Oct 29-Nov 4;329(6142):836-8
2823146
Eur J Pharmacol. 1987 Nov 24;144(1):109-11
2830117
Eur J Pharmacol. 1988 Jul 7;151(2):353-4
2844560