Solution structure of an immunoactive peptide fragment of Staphylococcal protein-A.
Staphylococcal protein-A (SpA) is known to bind the Fc fragment of immunoglobin G in vitro and induce a myriad of immunogenic responses in vivo. The latter is ascribed to be due to the interaction of Fc and SpA. It has also been proposed that in vivo proteolytically cleaved fragments of SpA may be functioning in the same manner. One such fragment (EQQNAFYEILHLPNLNEEQR), fragment 8-27 of the B-domain (SpA-B), was recently shown to exhibit in vivo immunogenic response [Sinha, P., Sengupta, J., and Ray, P. K. (1999) Biochem. Biophys. Res. Commun. 258, 141-147]. As a first step towards understanding the mode of interaction of this peptide with the Fc fragment, we have studied the solution conformation of this isolated peptide by CD and NMR. The peptide, with 7 contact residues in the crystal structure of the SpA-B/Fc complex and comprising of mostly helixI and part of helixII of the 3-helix bundle of SpA-B, was found to be present predominantly in extended structure. However it showed nascent turn/helix like conformations around F14 & Y15. These two residues are known to play a vital role in SpA-B/Fc interaction as deciphered from crystal structure and NMR studies of SpA-B/Fc complex and mutational studies. The implications of our results, especially the nascent conformations found around F14 & Y15, in design of SpA-B mimetic small molecules are discussed.
Sengupta
J
J
Department of Biophysics, Bose Institute, Calcutta, India.
Ray
P K
PK
Basu
G
G
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology; D002942:Circular Dichroism; D007536:Isomerism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D011392:Proline / Q000737:chemistry; D017433:Protein Structure, Secondary; D012996:Solutions; D013205:Staphylococcal Protein A / Q000737:chemistry* / Q000276:immunology; D013210:Staphylococcus / Q000276:immunology
D000907:Antibodies, Bacterial; D010446:Peptide Fragments; D012996:Solutions; D013205:Staphylococcal Protein A; D011392:Proline