The disulfide bond pattern of catrocollastatin C, a disintegrin-like/cysteine-rich protein isolated from Crotalus atrox venom

• Published in: Protein science Vol. 9; no. 7; pp. 1365 - 1373
• Main Authors: CALVETE, JUAN J., MORENO-MURCIANO, M. PAZ, SANZ, LIBIA, JÜRGENS, MICHAEL, SCHRADER, MICHAEL, RAIDA, MANFRED, BENJAMIN, DAVID C., FOX, JAY W.
• Format: Journal Article
• Language: English
• Published: Bristol Cambridge University Press 01.07.2000; Cold Spring Harbor Laboratory Press
• Subjects: ADAM; Amino Acid Motifs; Amino Acid Sequence; Animals; catrocollastatin‐C; Crotalid Venoms - chemistry; Crotalus; Cysteine; cysteine‐rich domain; Disintegrins - chemistry; disintegrin‐like domain; disulfide bond pattern; Disulfides - chemistry; mass spectrometry; Metalloendopeptidases - chemistry; Molecular Sequence Data; Reprolysin protein family; snake venom protein; ADAM; disintegrin-like domain; disulfide bond pattern; mass spectrometry; catrocollastatin-C; cysteine-rich domain; Reprolysin protein family; snake venom protein
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1110/ps.9.7.1365

The disulfide bond pattern of catrocollastatin-C was determined by N-terminal sequencing and mass spectrometry. The N-terminal disintegrin-like domain is a compact structure including eight disulfide bonds, seven of them in the same pattern as the disintegrin bitistatin. The protein has two extra cysteine residues (XIII and XVI) that form an additional disulfide bond that is characteristically found in the disintegrin-like domains of cellular metalloproteinases (ADAMs) and PIII snake venom Zn-metalloproteinases (SVMPs). The C-terminal cysteine-rich domain of catrocollastatin-C contains five disulfide bonds between nearest-neighbor cysteines and a long range disulfide bridge between CysV and CysX. These results provide structural evidence for a redefinition of the disintegrin-like and cysteine-rich domain boundaries. An evolutionary pathway for ADAMs, PIII, and PII SVMPs based on disulfide bond engineering is also proposed.