Crystallographic Complexes of Surfactant Protein A and Carbohydrates Reveal Ligand-induced Conformational Change (original) (raw)

2011, Journal of Biological Chemistry

D-mannose, D-␣-methylmannose, and glycerol, which represent subdomains of glycans on pathogen surfaces. Comparison of these complexes with the unliganded SP-A neck and carbohydrate recognition domain revealed an unexpected ligand-associated conformational change in the loop region surrounding the lectin site, one not previously reported for the lectin homologs SP-D and mannan-binding lectin. The net result of the conformational change is that the SP-A lectin site and the surrounding loop region become more compact. The Glu-202 side chain of unliganded SP-A extends out into the solvent and away from the calcium ion; however, in the complexes, the Glu-202 side chain translocates 12.8 Å to bind the calcium. The availability of Glu-202, together with positional changes involving water molecules, creates a more favorable hydrogen bonding environment for carbohydrate ligands. The Lys-203 side chain reorients as well, extending outward into the solvent in the complexes, thereby opening up a small cation-friendly cavity occupied by a sodium ion. Binding of this cation brings the large loop, which forms one wall of the lectin site, and the adjacent small loop closer together. The ability to undergo conformational changes may help SP-A adapt to different ligand classes, including microbial glycolipids and surfactant lipids. Surfactant protein A (SP-A) 2 is an abundant protein associated with pulmonary surfactant. Together with the lung pro-* This work was supported, in whole or in part, by National Institutes of Health Grant AI083222 from NIAID (to B. A. S.). This work was also supported by a Department of Veterans Affairs merit award (to F. X. M.). The atomic coordinates and structure factors (codes 3PAK, 3PAQ, 3PAR, and 3PBF) have been deposited in the Protein . 2 The abbreviations used are: SP-A, surfactant protein A; MBP, mannosebinding protein; CRD, carbohydrate recognition domain; NCRD, neck and carbohydrate recognition domain; ␣-MMA, ␣-methyl-D-mannoside; r.m.s.d., root mean square deviation. http://www.jbc.org/ Downloaded from FIGURE 4. Comparison of SP-A complex and native structures. Upper, stereo diagram of the C␣ trace of the SP-A NCRD⅐mannose complex (green) superimposed on the unliganded SP-A NCRD (orange). Middle and lower, stereo diagrams of an electron density map calculated with Fourier coefficients F o Ϫ F c of unliganded SP-A (middle) at 2.3 Å resolution and the SP-A⅐mannose complex (lower), omitting atoms from residues 197-203 from the calculation. The lectin calcium and sodium ions are shown as yellow and gray spheres, respectively.