Heparin-Binding Growth-Associated Molecule Contains Two Heparin Binding b-Sheet Domains That Are Homologous to the Thrombospondin Type I Repeat

Authors
Kilpeläinen, I.
Kaksonen, M.
Kinnunen, T.
Avikainen, H.
Linhardt, Robert J.
Fath, M.
Raulo, E.
Rauvala, H.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2000
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Terms of Use
Attribution 3.0 United States
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Full Citation
Heparin-Binding Growth-Associated Molecule Contains Two Heparin Binding b-Sheet Domains That Are Homologous to the Thrombospondin Type I Repeat I. Kilpeläinen, M. Kaksonen, T. Kinnunen, H. Avikainen, R.J. Linhardt, M. Fath, E. Raulo, H. Rauvala, Journal of Biological Chemistry, 275, 13564-13570, 2000.
Abstract
Heparin-binding growth-associated molecule (HB-GAM) is an extracellular matrix-associated protein implicated in the development and plasticity of neuronal connections of brain. Binding to cell surface heparan sulfate is indispensable for the biological activity of HB-GAM. In the present paper we have studied the structure of recombinant HB-GAM using heteronuclear NMR. These studies show that HB-GAM contains two β-sheet domains connected by a flexible linker. Both of these domains contain three antiparallel β-strands. In addition to this domain structure, HB-GAM contains the N- and C-terminal lysine-rich sequences that lack a detectable structure and appear to form random coils. Studies using CD and NMR spectroscopy suggest that HB-GAM undergoes a conformational change upon binding to heparin, and that the binding occurs primarily to the β-sheet domains of the protein. Search of sequence data bases shows that the β-sheet domains of HB-GAM are homologous to the thrombospondin type I repeat (TSR). Sequence comparisions show that the β-sheet structures found previously in midkine, a protein homologous with HB-GAM, also correspond to the TSR motif. We suggest that the TSR sequence motif found in various extracellular proteins defines a β-sheet structure similar to that found in HB-GAM and midkine. In addition to the apparent structural similarity, a similarity in biological functions is suggested by the occurrence of the TSR sequence motif in a wide variety of proteins that mediate cell-to-extracellular matrix and cell-to-cell interactions, in which the TSR domain mediates specific cell surface binding.
Description
Journal of Biological Chemistry, 275, 13564-13570
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Esevier
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
Access
Open Access
CC BY — Creative Commons Attribution