1pw9
From Proteopedia
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High resolution crystal structure of an active recombinant fragment of human lung surfactant protein D
Overview
Lung surfactant protein D (SP-D) can directly interact with carbohydrate, residues on pulmonary pathogens and allergens, stimulate immune cells, and, manipulate cytokine and chemokine profiles during the immune response in, the lungs. Therapeutic administration of rfhSP-D, a recombinant, homotrimeric fragment of human SP-D comprising the alpha-helical, coiled-coil neck plus three CRDs, protects mice against lung allergy and, infection caused by the fungal pathogen Aspergillus fumigatus. The high, resolution crystal structures of maltose-bound rfhSP-D to 1.4A, and of, rfhSP-D to 1.6A, define the fine detail of the mode and nature of, carbohydrate recognition and provide insights into how a small fragment of, human SP-D can bind to allergens/antigens or whole pathogens, and at the, same time recruit and engage effector cells and molecules of humoral, immunity. A previously unreported calcium ion, located on the trimeric, axis in a pore at the bottom of the funnel formed by the three CRDs and, close to the neck-CRD interface, is coordinated by a triad of glutamate, residues which are, to some extent, neutralised by their interactions with, a triad of exposed lysine residues in the funnel. The spatial relationship, between the neck and the CRDs is maintained internally by these lysine, residues, and externally by a glutamine, which forms a pair of, hydrogen-bonds within an external cleft at each neck-CRD interface., Structural links between the central pore and the cleft suggest a possible, effector mechanism for immune cell surface receptor binding in the, presence of bound, extended natural lipopolysaccharide and phospholipid, ligands. The structural requirements for such an effector mechanism, involving both the trimeric framework for multivalent ligand binding and, recognition sites formed from more than one subunit, are present in both, native hSP-D and rfhSP-D, providing a possible explanation for the, significant biological activity of rfhSP-D.
About this Structure
1PW9 is a Single protein structure of sequence from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.
Reference
High-resolution structural insights into ligand binding and immune cell recognition by human lung surfactant protein D., Shrive AK, Tharia HA, Strong P, Kishore U, Burns I, Rizkallah PJ, Reid KB, Greenhough TJ, J Mol Biol. 2003 Aug 8;331(2):509-23. PMID:12888356
Page seeded by OCA on Mon Nov 12 18:47:43 2007
