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A recombinant two-module form of human properdin is an inhibitor of the complement alternative pathway

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posted on 13.09.2016, 08:27 by Lubna Kouser, Munirah Abdul-Aziz, Anthony G. Tsolaki, Dipti Singhal, Wilhelm J. Schwaeble, Britta C. Urban, Haseeb A. Khan, Robert B. Sim, Uday Kishore
Properdin upregulates the alternative complement pathway by binding and stabilising the C3 convertase complex (C3bBb). Properdin is a soluble glycoprotein and its flexible rod-like 53kDa monomers form cyclic polymers (dimers, trimers, tetramers and pentamers). The properdin monomer consists of seven thrombospondin type I repeats (TSR 0-6), which are similar and homologous to domains found in circumsporozoite and thrombospondin-related anonymous proteins of Plasmodium species, ETP100 of Eimeria tenella, various complement components C6-C9, and thrombospondin I and II. Using deletion constructs, TSR4 and TSR5 of human properdin were implicated in C3b binding and stabilising C3 convertase. However, individually expressed TSR4 or TSR5 failed to bind properdin ligands. Here, we have expressed and characterized biologically active TSR4 and TSR5 together (TSR4+5) in tandem in Escherichia coli, fused to maltose-binding protein. MBP-TSR4+5 bind solid-phase C3b, sulfatides and glycosaminoglycans. In addition, functionally active recombinant TSR4+5 modules inhibit the alternative pathway of complement.

History

Citation

Molecular Immunology, 2016, 73, pp. 76-87

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Molecular Immunology

Publisher

Elsevier

issn

0161-5890

eissn

1872-9142

Acceptance date

07/03/2016

Copyright date

2016

Available date

13/09/2016

Publisher version

http://www.sciencedirect.com/science/article/pii/S0161589016300335

Language

en

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