Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods

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García-Jiménez, María José and Gil-Caballero, Sergio and Canales Mayordomo, Ángeles and Jiménez-Barbero, Jesús and de Paz, José L. and Nieto, Pedro M. (2017) Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods. International Journal of Molecular Sciences, 18 (6). p. 1293. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms18061293




Abstract

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.


Item Type:Article
Uncontrolled Keywords:NMR; FGF-1; STD-NMR; transient complexes
Subjects:Sciences > Chemistry > Chemistry, Organic
ID Code:66286
Deposited On:22 Jun 2021 15:26
Last Modified:23 Jun 2021 06:51

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