tailieunhanh - Báo cáo khoa học: Biochemical properties of the human guanylate binding protein 5 and a tumor-specific truncated splice variant Mark Wehner and Christian Herrmann

The human guanylate binding protein 5 (hGBP5) belongs to the family of interferon-c-inducible large GTPases, which are well known for their high induction by pro-inflammatory cytokines. The cellular role of this protein family is unclear at this point, but there are indications for antiviral and antibacterial activity of hGBP1. | ỊFEBS Journal Biochemical properties of the human guanylate binding protein 5 and a tumor-specific truncated splice variant Mark Wehner and Christian Herrmann Ruhr-Universitat Bochum Physikalische Chemie I - AG Proteininteraktionen UniverstitatsstraBe 150 Bochum Germany Keywords biophysics dynamin GTPase guanylate binding protein interferons Correspondence C. Herrmann Ruhr-Universitat Bochum Physikalische Chemie I - AG Proteininteraktionen UniversitatsstraBe 150 44800 Bochum Germany Fax 49 2343214785 Tel 49 2343224173 E-mail Received 9 October 2009 revised 15 January 2010 accepted 19 January 2010 doi The human guanylate binding protein 5 hGBP5 belongs to the family of interferon-y-inducible large GTPases which are well known for their high induction by pro-inflammatory cytokines. The cellular role of this protein family is unclear at this point but there are indications for antiviral and antibacterial activity of hGBP1. hGBP5 exists in three splice variants forming two different proteins of which the tumor-specific one is C-terminally truncated by 97 amino acids and therefore lacks the CaaX motif for gera-nylgeranylation. Here we present biochemical data on the splice variants of hGBP5. We show that unlike hGBP1 hGBP5a b and hGBP5ta do not bind GMP or produce any GMP during hydrolysis despite the fact the residues involved in GMP production from hGBP1 are conserved in hGBP5. Hydrolysis of GTP is concentration-dependent and shows weak self-activation. Thermodynamic studies showed strongly negative entropic changes during nucleotide binding which reflect structural ordering in the protein during nucleotide binding. These structural changes were also observed during changes in the oligomerization state. We observed only a minor influence of the C-terminal truncation on hydrolysis nucleotide binding and oligomerization of hGBP5. Based on these similarities we speculate that the missing C-terminal part which also .