title: Molecular basis of the interaction between proapoptotic truncated BID (tBID) protein and mitochondrial carrier homologue 2 (MTCH2) protein: key players in mitochondrial death pathway.
abstract: The molecular basis of the interaction between mitochondrial carrier homologue 2 (MTCH2) and truncated BID (tBID) was characterized. These proteins participate in the apoptotic pathway, and the interaction between them may serve as a target for anticancer lead compounds. In response to apoptotic signals, MTCH2 recruits tBID to the mitochondria, where it activates apoptosis. A combination of peptide arrays screening with biochemical and biophysical techniques was used to characterize the mechanism of the interaction between tBID and MTCH2 at the structural and molecular levels. The regions that mediate the interaction between the proteins were identified. The two specific binding sites between the proteins were determined to be tBID residues 59-73 that bind MTCH2 residues 140-161, and tBID residues 111-125 that bind MTCH2 residues 240-290. Peptides derived from tBID residues 111-125 and 59-73 induced cell death in osteosarcoma cells. These peptides may serve as lead compounds for anticancer drugs that act by targeting the tBID-MTCH2 interaction.
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Safra Campus, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Katz
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Zaltsman-Amir
authors.forename: Yana
authors.initials: Y
authors.lastname: Mostizky
authors.forename: Neta
authors.initials: N
authors.lastname: Kollet
authors.forename: Atan
authors.initials: A
authors.lastname: Gross
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D040081:Protein Array Analysis
chemical_list: D000970:Antineoplastic Agents; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C502207:MTCH2 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D010455:Peptides