Gas-Phase Examination of the Complex of Fibroblast Growth Factor 1 with Heparan Sulfate: a Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study

Authors
Zhao, Y.
Singh, A.
Xu, Y.
Zong, C.
Zhang, F.
Boons, G.J.
Liu, J.
Linhardt, Robert J.
Woods, R.J.
Amster, I.J.
ORCID
https://orcid.org/0000-0003-2219-5833
Loading...
Thumbnail Image
Other Contributors
Issue Date
2017
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
Full Citation
Gas-Phase Examination of the Complex of Fibroblast Growth Factor 1 with Heparan Sulfate: a Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study, Y. Zhao, A. Singh, Y. Xu, C. Zong, F. Zhang, G.-J. Boons, J. Liu, R. J. Linhardt, R. J. Woods, I. J. Amster, Journal of the American Society of Mass Spectrometry, 28, 96-109, 2017.
Abstract
Fibroblast growth factors (FGFs) regulate several cellular developmental processes by interacting with cell surface heparan proteoglycans and transmembrane cell surface receptors (FGFR). The interaction of FGF with heparan sulfate (HS) is known to induce protein oligomerization, increase the affinity of FGF towards its receptor FGFR, promoting the formation of the HS–FGF–FGFR signaling complex. Although the role of HS in the signaling pathways is well recognized, the details of FGF oligomerization and formation of the ternary signaling complex are still not clear, with several conflicting models proposed in literature. Here, we examine the effect of size and sulfation pattern of HS upon FGF1 oligomerization, binding stoichiometry and conformational stability, through a combination of ion mobility (IM) and theoretical modeling approaches. Ion mobility-mass spectrometry (IMMS) of FGF1 in the presence of several HS fragments ranging from tetrasaccharide (dp4) to dodecasaccharide (dp12) in length was performed. A comparison of the binding stoichiometry of variably sulfated dp4 HS to FGF1 confirmed the significance of the previously known high-affinity binding motif in FGF1 dimerization, and demonstrated that certain tetrasaccharide-length fragments are also capable of inducing dimerization of FGF1. The degree of oligomerization was found to increase in the presence of dp12 HS, and a general lack of specificity for longer HS was observed. Additionally, collision cross-sections (CCSs) of several FGF1–HS complexes were calculated, and were found to be in close agreement with experimental results. Based on the (CCSs) a number of plausible binding modes of 2:1 and 3:1 FGF1–HS are proposed.
Description
Journal of the American Society of Mass Spectrometry, 28, 96-109
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
American Chemical Society (ACS)
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
Access
A full text version is available in DSpace@RPI