Solution structure of the coiled-coil trimerization domain from lung surfactant protein D.
Surfactant protein D (SP-D) is one of four known protein components of the pulmonary surfactant lining the lung alveoli. It is involved in immune and allergic responses. SP-D occurs as a tetramer of trimers. Trimerization is thought to be initiated by a coiled coil domain. We have determined the solution structure of a 64-residue peptide encompassing the coiled coil domain of human SP-D. As predicted, the domain forms a triple-helical parallel coiled coil. As with all symmetric oligomers, the structure calculation was complicated by the symmetry degeneracy in the NMR spectra. We used the symmetry-ADR (ambiguous distance restraint) structure calculation method to solve the structure. The results demonstrate that the leucine zipper region of SP-D is an autonomously folded domain. The structure is very similar to the independently determined X-ray crystal structure, differing mainly at a single residue, Tyr248. This residue is completely symmetric in the solution structure, and markedly asymmetric in the crystalline phase. This difference may be functionally important, as it affects the orientation of the antigenic surface presented by SP-D.
Kovacs
Helena
H
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
O'Ddonoghue
Sean I
SI
Hoppe
Hans-Jürgen
HJ
Comfort
David
D
Reid
Kenneth B M
KB
Campbell
lain D
lD
Nilges
Michael
M
D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry; D020449:Repetitive Sequences, Amino Acid; D012996:Solutions
D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D012996:Solutions