Open AccessRecombinant hemangiopoietin promotes cell adhesion and binds heparin in its multimeric form
Author(s) -
Lifang Wang,
Zhibo Han,
Mei Li,
Ping Yang,
Bin Xv,
JiPing Zhang,
Han Han
Publication year - 2013
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2013.1274
Subject(s) - tetramer , recombinant dna , multiprotein complex , microbiology and biotechnology , biochemistry , biology , cell adhesion , cell , chemistry , gene , enzyme
Hemangiopoietin (HAPO) is a novel growth factor stimulating the proliferationof hematopoietic and endothelial progenitor cells in vitro and in vivo. The nativeprotein is a 294‑amino acid multimodular protein. The N‑terminus constitutes oftwo somatomedin B (SMB) homology domains that contain 14 cysteines. The centralregion is a putative heparin‑binding domain (pHBD) and the C‑terminus containsmucin‑like repeats. In the present study, we demonstrated that prokaryotic recombinanthuman HAPO (rhHAPO) self‑associates into a multimeric form with a mass weightof ~129 kDa, suggesting a homologous tetramer. rhHAPO in its multimeric form wasfound to be more stable and more potent in promoting HESS‑5 cell adhesion. MultimericrhHAPO had a higher affinity to heparin compared with its dimeric form, althoughthere was no significant conformational change. C‑terminal repeats-truncated rhHAPO(rhHAPOΔmucin) was also found to be assembled into a multimer, while deletionof pHBD (rhHAPOΔmucin‑pHBD) caused the protein to remain in a dimeric form, demonstratingthat SMB domains participate in self‑aggregation of the molecule and that thepHBD region promotes the tetramerization.