NMR structures of the C-terminal end of human complement serine protease C1s.
Synthetic peptides derived from the C-terminal end of the human complement serine protease C1s were analysed by circular dichroism and nuclear magnetic resonance (NMR) spectroscopy. Circular dichroism indicates that peptides 656-673 and 653-673 are essentially unstructured in water and undergo a coil-to-helix transition in the presence of increasing concentrations of trifluoroethanol. Two-dimensional NMR analyses performed in water/trifluoroethanol solutions provide evidence for the occurrence of a regular alpha-helix extending from Trp659 to Ser668 (peptide 656-673), and from Tyr656 to Ser668 (peptide 653-673), the C-terminal segment of both peptides remaining unstructured under the conditions used. Based on these and other observations, we propose that the serine protease domain of C1s ends in a 13-residue alpha-helix (656Tyr-Ser668) followed by a five-residue C-terminal extension. The latter appears to be flexible and is probably locked within C1s through a salt bridge involving Glu672.
Gans
P
P
Laboratoire de Résonance Magnétique Nucleéaire, Institut de Biologie Structurale Jean-Pierre Ebel (CEA/CNRS), Cedex, France.
Rossi
V
V
Gaboriaud
C
C
Bally
I
I
Hernandez
J F
JF
Blackledge
M J
MJ
Arlaud
G J
GJ
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003173:Complement C1s / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014270:Trifluoroethanol / Q000494:pharmacology
D010446:Peptide Fragments; D014270:Trifluoroethanol; D003173:Complement C1s