Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/101145
Title: Molecular interfaces of the galactose-binding protein tectonin domains in host-pathogen interaction
Authors: Low, D.H.P.
Frecer, V.
Le Saux, A. 
Srinivasan, G.A. 
Ho, B.
Chen, J.
Ding, J.L. 
Issue Date: 26-Mar-2010
Citation: Low, D.H.P., Frecer, V., Le Saux, A., Srinivasan, G.A., Ho, B., Chen, J., Ding, J.L. (2010-03-26). Molecular interfaces of the galactose-binding protein tectonin domains in host-pathogen interaction. Journal of Biological Chemistry 285 (13) : 9898-9907. ScholarBank@NUS Repository.
Abstract: β-Propeller proteins function in catalysis, protein-protein interaction, cell cycle regulation, and innate immunity. The galactose-binding protein (GBP) from the plasma of the horse-shoe crab, Carcinoscorpius rotundicauda, is a β-propeller protein that functions in antimicrobial defense. Studies have shown that upon binding to Gram-negative bacterial lipopolysaccharide (LPS), GBP interacts with C-reactive protein (CRP) to form a pathogen-recognition complex, which helps to eliminate invading microbes. However, the molecular basis of interactions between GBP and LPS and how it interplays with CRP remain largely unknown. By homology modeling, we showed that GBP contains six β-propeller/Tectonin domains. Ligand docking indicated that Tectonin domains 6 to 1 likely contain the LPS binding sites. Protein-protein interaction studies demonstrated that Tectonin domain 4 interacts most strongly with CRP. Hydrogen-deuterium exchange mass spectrometry mapped distinct sites of GBP that interact with LPS and with CRP, consistent with in silico predictions. Furthermore, infection condition (lowered Ca 2+ level) increases GBP-CRP affinity by 1000-fold. Resupplementing the system with a physiological level of Ca2+ did not reverse the protein-protein affinity to the basal state, suggesting that the infection-induced complex had undergone irreversible conformational change. We propose that GBP serves as a bridging molecule, participating in molecular interactions, GBP-LPS and GBP-CRP, to form a stable pathogen-recognition complex. The interaction interfaces in these two partners suggest that Tectonin domains can differentiate self/nonself, crucial to frontline defense against infection. In addition, GBP shares architectural and functional homologies to a human protein, hTectonin, suggesting its evolutionarily conservation for ∼500 million years, from horseshoe crab to human. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/101145
ISSN: 00219258
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

13
checked on May 10, 2018

WEB OF SCIENCETM
Citations

13
checked on May 16, 2018

Page view(s)

30
checked on Jul 6, 2018

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.