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

PDB id:

1pwb

Name:

Signaling protein

Title:

High resolution crystal structure of an active recombinant fragment of human lung surfactant protein d with maltose

Structure:

Pulmonary surfactant-associated protein d. Chain: a, b, c. Fragment: recombinant fragment. Synonym: sp-d, psp-d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Trimer (from PQS)

Resolution:

1.40Å R-factor: 0.205 R-free: 0.228

Authors:

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

Key ref:

A.K.Shrive et al. (2003). High-resolution structural insights into ligand binding and immune cell recognition by human lung surfactant protein D. J Mol Biol, 331, 509-523. PubMed id: 12888356 DOI: 10.1016/S0022-2836(03)00761-7

Date:

01-Jul-03 Release date: 05-Aug-03

Protein chains

P35247  (SFTPD_HUMAN) -  Pulmonary surfactant-associated protein D from Homo sapiens

Seq: 375 a.a.

Struc: 151 a.a.

DOI no: 10.1016/S0022-2836(03)00761-7

J Mol Biol 331:509-523 (2003)

PubMed id: 12888356

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

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

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.

Selected figure(s)

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.

Figures were selected by the author.