Proton NMR studies of human C3a anaphylatoxin in solution: Sequential resonance assignments, secondary structure, and global fold

Journal Article · Tue Dec 27 04:00:00 EST 1988 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00426a011· OSTI ID:5404162

Chazin, W J; Hugli, T E; Wright, P E ^[1]

---

1. Research Institute of Scripps Clinic, La Jolla, CA (USA)

The spin systems that comprise the {sup 1}H nuclear magnetic resonance (NMR) spectrum of the complement fragment C3a (M{sub r} 8,900) 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 {sup 3}J{sub HN{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-Arg{sup 77}-C3a. Differences between the solution and crystal structures of C3a are observed, particularly in the N-terminal region. The relevance of these new observations is discussed with respect to physiologic responses that are elicited by the local hormone-like anaphylatoxin molecule.

• OSTI ID: 5404162
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 27:26; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANTIGENS
ARGININE
BARYONS
CARBOXYLIC ACIDS
COMPLEMENT
ELEMENTARY PARTICLES
FERMIONS
HADRONS
MAGNETIC RESONANCE
MATERIALS
MOLECULAR STRUCTURE
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OVERHAUSER EFFECT
PROTEINS
PROTONS
RESONANCE
SPECTRA
TOXIC MATERIALS
TOXINS