1H NMR studies of human C3a anaphylatoxin in solution: sequential resonance assignments, secondary structure, and global fold.

Chazin WJ, Hugli TE, Wright PE
Biochemistry. 1988 27 (26): 9139-48

PMID: 3266557 · DOI:10.1021/bi00426a011

The spin systems that comprise the 1H nuclear magnetic resonance (NMR) spectrum of the complement fragment C3a (Mr 8900) have been completely identified by an approach which integrates data from a wide range of two-dimensional NMR experiments. Both relayed and multiple quantum experiments play an essential role in the analysis. After the first stage of analysis the spin systems of 60 of the 77 residues were assigned to the appropriate residue type, providing an ample basis for subsequent sequence-specific assignments. Elements of secondary structure were identified on the basis of networks of characteristic sequential and medium-range nuclear Overhauser effects (NOEs), values of 3JHN alpha, and locations of slowly exchanging backbone amide protons. Three well-defined helical segments are found. Gradients of increasing mobility in distinct segments of the C3a polypeptide are observed, with very high mobilities for several residues near the C- and N-termini, including the complete C-terminal receptor binding site pentapeptide LGLAR. The NMR data, combined with known disulfide linkages and a small number of critical long-range NOEs, provide the global folding pattern of C3a in solution. Identical solution structures were found for both the intact active protein and the largely inactive physiologic product des-Arg77-C3a.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms (8)

Amino Acid Sequence Complement C3 Complement C3a Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Protein Conformation Solutions

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