PDBsum entry 1pwb

Signaling protein

PDB id: 1pwb

Contents

Protein chain

151 a.a. *

Ligands

GLC-GLC

GLC ×2

Metals

_CA ×9

Waters ×506

* Residue conservation analysis

References listed in PDB file

Key reference

Title

High-Resolution structural insights into ligand binding and immune cell recognition by human lung surfactant protein d.

Authors

A.K.Shrive, H.A.Tharia, P.Strong, U.Kishore, I.Burns, P.J.Rizkallah, K.B.Reid, T.J.Greenhough.

Ref.

J Mol Biol, 2003, 331, 509-523. [DOI no: 10.1016/S0022-2836(03)00761-7]

PubMed id

12888356

Abstract

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.

Figure 3.
Figure 3. The maltose-bound rfhSP-D trimer showing the bound maltose, the three calcium ions and the central asymmetric tyrosine C228 (generated using MOLSCRIPT.[39.]) (a) Viewed down the molecular 3-fold; (b) viewed perpendicular to the molecular 3-fold.

Figure 7.
Figure 7. Stereoviews (maltose-bound structure) of the neck-CRD interface and interactions. Chain A is in yellow, B in blue and C in red. (a) The interface between CRD A and neck C showing the asymmetric residues TyrC228 and LysA229. The LysC230-GlyA265 contact is present due only to a crystal contact (see the text). (b) The interface between CRD B and neck A showing the asymmetric GluB232 (maltose-bound structure only). The conformation of His220 differs from that in (a) due to a crystal contact. Figure generated using MOLSCRIPT.[39.]

The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 331, 509-523) copyright 2003.

Secondary reference #1

Title

Crystal structure of the trimeric alpha-Helical coiled-Coil and the three lectin domains of human lung surfactant protein d.

Authors

K.Håkansson, N.K.Lim, H.J.Hoppe, K.B.Reid.

Ref.

Structure, 1999, 7, 255-264. [DOI no: 10.1016/S0969-2126(99)80036-7]

PubMed id

10368295

Figure 7.
Figure 7. The mainchain fold of hSP-D with consensus motifs highlighted: DGGS is in red and RACGEKR is in blue. Calcium ions are depicted as green spheres. (The figure was produced using the program RIBBONS [39].)

The above figure is reproduced from the cited reference with permission from Cell Press