Solution structure of Hyp10Pro variant of conomarphin, a cysteine-free and D-amino-acid containing conopeptide.
Conotoxins are mainly disulfide-rich short peptides active on different ion channels, neurotransmitter receptors or transporters in nervous system, exhibiting highly diversified composition, structures and biological functions. Besides these kinds of conopeptides, some novel cysteine-free conopeptides have also been reported. Conomarphin, a cystine-free 15-residue conopeptide from Conus marmoreus, has been purified and classified into M-superfamily. In addition to its unique characteristic of a D-type phenylalanine at the third residue from the C-terminus, conomarphin has an unusual hydroxyproline residue at position 10. To make an effort to understand the role of hydroxyproline post-translational modification in conomarphin, (1)H NMR solution structure of Hyp10Pro variant of conomarphin was resolved and compared with the native conomarphin in the present work. The Hyp10Pro conomarphin has a type II-beta-turn near the C-terminus instead of a 3(10) helix in native conomarphin. The compact loop region in native conomarphin becomes more open when hydroxyproline is displaced by proline. This reveals that hydroxyproline residue is essential for the structure of conomarphin just like D-Phe13. The unusual post-translational modification of conomarphin implies a unique selectivity of hydroxylation in toxin sequence.
Huang
Feijuan
F
Department of Chemistry, Renmin University of China, 59 Zhong Guan Cun Street, Beijing 100872, PR China.
Du
Weihong
W
D000596:Amino Acids / Q000032:analysis / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D020916:Conotoxins / Q000737:chemistry*; D052078:Conus Snail / Q000737:chemistry*; D003545:Cysteine / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008978:Mollusk Venoms / Q000737:chemistry*; D011487:Protein Conformation
D000596:Amino Acids; D020916:Conotoxins; D008978:Mollusk Venoms; C529778:conomarphin, Conus marmoreus; D003545:Cysteine