Solution conformation of carboxy-terminal fragments of the third component of human complement C3: proton nuclear magnetic resonance study of C3a, des-Arg-C3a, and C3a Arg69.
A proton nuclear magnetic resonance (NMR) study is reported of the solution conformation of human C3a, that is released on activation of C3, the third component of complement. The intact C3a was used along with des-Arg-C3a, which is formed on cleavage of Arg-77 at the C terminal of C3a, and C3a Arg69, which is a 69-residue fragment produced on tryptic digestion of C3. A method of carboxypeptidase digestion/difference spectroscopy (Endo & Arata (1985) Biochemistry 24, 1561-1568) was extensively used for the spectral assignments of Ile-43, Ile-60, Leu-63, Tyr-15, and Tyr-59. On the basis of the results of nuclear Overhauser effect (NOE) measurements, we discuss the solution conformation of the C3a molecule. It has been concluded that removal of Arg-77, which is essential for expression of the biological activity of C3a, does not induce any significant change in the solution conformation of the C3a molecule. The C3a molecule is known to consist of a core region that comprises segment Tyr-15-Tyr-59. We conclude that in solution the C terminal segment sticks out of the core and takes on a helix-like conformation. Possible roles of the core region and the N terminal segment in maintaining the conformation of the C terminal segment are briefly discussed.
D000595:Amino Acid Sequence; D001120:Arginine; D002851:Chromatography, High Pressure Liquid; D003176:Complement C3 / Q000032:analysis*; D015926:Complement C3a; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation
D003176:Complement C3; D015926:Complement C3a; D001120:Arginine