Heparin-binding growth-associated molecule contains two heparin-binding β-sheet domains that are homologous to the thrombospondin type I repeat
Heparin-binding growth-associated molecule contains two heparin-binding β-sheet domains that are homologous to the thrombospondin type I repeat
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DOI：
10.1074/jbc.275.18.13564
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发表时间：
2000-05-05
影响因子：
4.8
通讯作者：
Rauvala, H
中科院分区：
文献类型：
--
作者：
Kilpeläinen, I;Kaksonen, M;Rauvala, H
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-GAIM using heteronuclear NMR. These studies show that HB-GARI contains two beta-sheet domains connected by a flexible linker. Both of these domains contain three antiparallel beta-strands, In addition to this domain structure, HB-GAM contains the Nand 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-GAIM undergoes a conformational change upon binding to heparin, and that the binding occurs primarily to the beta-sheet domains of the protein. Search of sequence data bases shows that the beta-sheet domains of HB-GAM are homologous to the thrombospondin type I repeat (TSR), Sequence comparisions show that the beta-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 beta-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.
