Imperial College London
Alternate

DrWengangChai

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2596w.chai

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ribeiro:2019:10.1111/febs.15162,
author = {Ribeiro, DO and Viegas, A and Pires, VMR and Medeiros-Silva, J and Bule, P and Chai, W and Marcelo, F and Fontes, CMGA and Cabrita, EJ and Palma, AS and Carvalho, AL},
doi = {10.1111/febs.15162},
journal = {The Federation of European Biochemical Societies (FEBS) Journal},
pages = {2723--2743},
title = {Molecular basis for the preferential recognition of beta 1,3-1,4-glucans by the family 11 carbohydrate-binding module from Clostridium thermocellum},
url = {http://dx.doi.org/10.1111/febs.15162},
volume = {287},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Understanding the specific molecular interactions between proteins and β1,3-1,4-mixed-linked d-glucans is fundamental to harvest the full biological and biotechnological potential of these carbohydrates and of proteins that specifically recognize them. The family 11 carbohydrate-binding module from Clostridium thermocellum (CtCBM11) is known for its binding preference for β1,3-1,4-mixed-linked over β1,4-linked glucans. Despite the growing industrial interest of this protein for the biotransformation of lignocellulosic biomass, the molecular determinants of its ligand specificity are not well defined. In this report, a combined approach of methodologies was used to unravel, at a molecular level, the ligand recognition of CtCBM11. The analysis of the interaction by carbohydrate microarrays and NMR and the crystal structures of CtCBM11 bound to β1,3-1,4-linked glucose oligosaccharides showed that both the chain length and the position of the β1,3-linkage are important for recognition, and identified the tetrasaccharide Glcβ1,4Glcβ1,4Glcβ1,3Glc sequence as a minimum epitope required for binding. The structural data, along with site-directed mutagenesis and ITC studies, demonstrated the specificity of CtCBM11 for the twisted conformation of β1,3-1,4-mixed-linked glucans. This is mediated by a conformation–selection mechanism of the ligand in the binding cleft through CH-π stacking and a hydrogen bonding network, which is dependent not only on ligand chain length, but also on the presence of a β1,3-linkage at the reducing end and at specific positions along the β1,4-linked glucan chain. The understanding of the detailed mechanism by which CtCBM11 can distinguish between linear and mixed-linked β-glucans strengthens its exploitation for the design of new biomolecules with improved capabilities and applications in health and agriculture.
AU  - Ribeiro,DO
AU  - Viegas,A
AU  - Pires,VMR
AU  - Medeiros-Silva,J
AU  - Bule,P
AU  - Chai,W
AU  - Marcelo,F
AU  - Fontes,CMGA
AU  - Cabrita,EJ
AU  - Palma,AS
AU  - Carvalho,AL
DO  - 10.1111/febs.15162
EP  - 2743
PY  - 2019///
SN  - 1742-464X
SP  - 2723
TI  - Molecular basis for the preferential recognition of beta 1,3-1,4-glucans by the family 11 carbohydrate-binding module from Clostridium thermocellum
T2  - The Federation of European Biochemical Societies (FEBS) Journal
UR  - http://dx.doi.org/10.1111/febs.15162
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000503256200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15162
VL  - 287
ER  -
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