PDBsum entry 1w0r

Glycoprotein

PDB id

1w0r

Contents

			Protein chains

					442 a.a.*

* C-alpha coords only

References listed in PDB file

Key reference

Title

The dimeric and trimeric solution structures of the multidomain complement protein properdin by X-Ray scattering, Analytical ultracentrifugation and constrained modelling.

Authors

Z.Sun, K.B.Reid, S.J.Perkins.

Ref.

J Mol Biol, 2004, 343, 1327-1343. [DOI no: 10.1016/j.jmb.2004.09.001]

PubMed id

15491616

Abstract

Properdin regulates the alternative pathway of the complement system of immune defence by stabilising the C3 convertase complex. It contains six thrombospondin repeat type I (TSR-1 to TSR-6) domains and an N-terminal domain. Properdin exists as either a dimer, trimer or tetramer. In order to determine the solution structure of multiple TSR domains, the molecular structures of dimeric and trimeric properdin were studied by X-ray scattering and analytical ultracentrifugation. Guinier analyses showed that the dimer and trimer have radii of gyration R(G) values of 7.5 nm and 10.3 nm, respectively, and cross-sectional radii of gyration R(XS) values of 1.3 nm and 1.5 nm, respectively. Distance distribution functions showed that the maximum lengths of the dimer and trimer were 25 nm and 30 nm, respectively. Analytical ultracentrifugation gave sedimentation coefficients of 5.1S and 5.2S for the dimer and trimer forms, respectively. Homology models for the TSR domains were constructed using the crystal structure of the TSP-2 and TSP-3 domains in human thrombospondin as templates. Properdin could be represented by seven TSR domains, not six as believed, since the crystal structure determined for TSP-2 and TSP-3 showed that the N-terminal domain (TSR-0) could be represented by a truncated TSR domain with the same six conserved Cys residues found in TSR-1 to TSR-6. Automated constrained molecular modelling revealed the solution conformations of multiple TSR domains in properdin at medium resolution. The comparison of 3125 systematically generated conformational models for the trimer with the X-ray data showed that good curve fits could be obtained by assuming that the linker between adjacent TSR domains possessed limited flexibility. Good trimer models correspond to partially collapsed triangular structures, and extended triangular shapes do not fit the data. The corresponding 3125 models for the dimer revealed a similar outcome in which a partially collapsed TSR structure gave good fits. The models account for the effect of mutations that cause properdin deficiencies, and suggest that the biologically active TSR-4, TSR-5 and TSR-6 domains are exposed for protein-protein interactions. The role of the other TSR domains in properdin may be to act as spacers to make TSR-4, TSR-5 and TSR-6 accessible for function.



	Figure 1. Figure 1. Schematic cartoon of the TSR arrangement in the properdin dimer and trimer. The full-length TSR domains are numbered from TSR-1 to TSR-6, while the putative truncated N-terminal TSR domain is denoted by TSR-0. The location of the presumed N-linked glycosylation site on TSR-6 is denoted by a q symbol. Both these domain arrangements are drawn for clarity, however neither of these arrangements fit the scattering modelling (see Figure 8(b) and (d) below).		Figure 11. Figure 11. Electrostatic views of the properdin monomer. The extended model is shown for clarity. The blue and red colours denote positively and negatively charged surfaces, respectively. (a) Three views are shown of the four-domain N-terminal half, which is comprised of TSR-0 to TSR-3. The ribbon view showing the location of the TSR domains is shown to the left. The electrostatic surface view to the left corresponds to the view of the ribbon representation, while that to the right corresponds to an 180° rotation about the vertical axis. (b) Three views are shown likewise for the four-domain C-terminal half, which is comprised of TSR-3 to TSR-6.

	Headers