tailieunhanh - Báo cáo khoa học: Inhibitory effects of nontoxic protein volvatoxin A1 on pore-forming cardiotoxic protein volvatoxin A2 by interaction with amphipathic a-helix

Volvatoxin A2, a pore-forming cardiotoxic protein, was isolated from the edible mushroomVolvariella volvacea. Previous studies have demonstrated that volvatoxin A consists of volvatoxin A2 and volvatoxin A1, and the hemolytic activity of volvatoxin A2 is completely abolished by volvatoxin A1 at a volvatoxin A2⁄volvatoxin A1 molar ratio of 2. | iFEBS Journal Inhibitory effects of nontoxic protein volvatoxin A1 on pore-forming cardiotoxic protein volvatoxin A2 by interaction with amphipathic a-helix Pei-Tzu Wu1 Su-Chang Lin2 Chyong-Ing Hsu1 Yen-Chywan Liaw2 and Jung-Yaw Lin1 1 Institute of Biochemistry and Molecular Biology College of Medicine NationalTaiwan University Taipei Taiwan 2 Institute of Molecular Biology Academia Sinica Taipei Taiwan Keywords amphipathic a-helix co-pull-down experiment tandem repeat protein volvatoxin A1 volvatoxin A2 Correspondence . Lin Institute of Biochemistry and Molecular Biology College of Medicine NationalTaiwan University F9 no. 1 Section 1 Jen-Ai Road Taipei 10051 Taiwan Fax 886 2 23415334 Tel 886 2 23123456 ext. 8206 8207 E-mail jylin@ Database The nucleotide sequence reported in this paper has been submitted to the DDBJ EMBL GenBank databases under the accession number AY952461 Received 22 March 2006 revised 1 May 2006 accepted 17 May 2006 doi Volvatoxin A2 a pore-forming cardiotoxic protein was isolated from the edible mushroom Volvariella volvacea. Previous studies have demonstrated that volvatoxin A consists of volvatoxin A2 and volvatoxin A1 and the hemolytic activity of volvatoxin A2 is completely abolished by volvatoxin A1 at a volvatoxin A2 volvatoxin A1 molar ratio of 2. In this study we investigated the molecular mechanism by which volvatoxin A1 inhibits the cytotoxicity of volvatoxin A2. Volvatoxin A1 by itself was found to be nontoxic and furthermore it inhibited the hemolytic and cytotoxic activities of volvatoxin A2 at molar ratios of 2 or lower. Interestingly volvatoxin A1 contains 393 amino acid residues that closely resemble a tandem repeat of volvatoxin A2. Volvatoxin A1 contains two pairs of amphipathic a-heli-ces but it lacks a heparin-binding site. This suggests that volvatoxin A1 may interact with volvatoxin A2 but not with the cell membrane. By using confocal microscopy it was demonstrated .