Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
by
María José García-Jiménez 1, Sergio Gil-Caballero 1, Ángeles Canales 2, Jesús Jiménez-Barbero 3,4,5, José L. De Paz 1 and Pedro M. Nieto 1,*
María José García-Jiménez 1, Sergio Gil-Caballero 1, Ángeles Canales 2, Jesús Jiménez-Barbero 3,4,5, José L. De Paz 1 and Pedro M. Nieto 1,*
1
Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), Centro de Investigaciones Científicas Isla de La Cartuja, CSIC and Universidad de Sevilla, Américo Vespucio, 49, 41092 Sevilla, Spain
2
Complutense University of Madrid, Fac CC Quim, Department Quim Organ 1, Avd Complutense S/N, E-28040 Madrid, Spain
3
CIC bioGUNE, Bizkaia Technology Park, Building 801A, 48170 Derio, Spain
4
Basque Foundation for Science, Maria Diaz de Haro 13, 48009 Bilbao, Spain
5
Department of Organic Chemistry II, Faculty of Science and Technology, University of the Basque Country, 48940 Leioa, Bizkaia, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(6), 1293; https://doi.org/10.3390/ijms18061293
Received: 31 March 2017 / Revised: 11 June 2017 / Accepted: 12 June 2017 / Published: 17 June 2017
(This article belongs to the Special Issue Molecular Recognition of Carbohydrates)
FGF-1 is a potent mitogen that, by interacting simultaneously with Heparan Sulfate Glycosaminoglycan HSGAG and the extracellular domains of its membrane receptor (FGFR), generates an intracellular signal that finally leads to cell division. The overall structure of the ternary complex Heparin:FGF-1:FGFR has been finally elucidated after some controversy and the interactions within the ternary complex have been deeply described. However, since the structure of the ternary complex was described, not much attention has been given to the molecular basis of the interaction between FGF-1 and the HSGAG. It is known that within the complex, the carbohydrate maintains the same helical structure of free heparin that leads to sulfate groups directed towards opposite directions along the molecular axis. The precise role of single individual interactions remains unclear, as sliding and/or rotating of the saccharide along the binding pocket are possibilities difficult to discard. The HSGAG binding pocket can be subdivided into two regions, the main one can accommodate a trisaccharide, while the other binds a disaccharide. We have studied and analyzed the interaction between FGF-1 and a library of trisaccharides by STD-NMR and selective longitudinal relaxation rates. The library of trisaccharides corresponds to the heparin backbone and it has been designed to interact with the main subsite of the protein.
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Keywords:
NMR; FGF-1; STD-NMR; transient complexes
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MDPI and ACS Style
García-Jiménez, M.J.; Gil-Caballero, S.; Canales, Á.; Jiménez-Barbero, J.; De Paz, J.L.; Nieto, P.M. Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods. Int. J. Mol. Sci. 2017, 18, 1293.
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