Peptide Array Screening Reveals Molecular Basis of the Interaction Between Proapoptotic Proteins

Identification of medicinal compounds capable of inducing cancer cells to enter apoptosis is the goal of many drug development efforts.

Investigators at the Hebrew University of Jerusalem (Israel) studied the interaction between two proteins known to be elements of a molecular pathway leading to cell death. Details of how mitochondrial carrier homologue 2 (MTCH2) interacts with truncated BID (tBID) were reported in the April 27, 2012, issue of the Journal of Biological Chemistry.

A combination of peptide array screening along with biochemical and biophysical techniques was used to characterize the mechanism of the interaction between tBID and MTCH2 at the structural and molecular levels. Results revealed that in response to apoptotic signals, MTCH2 recruited tBID to the mitochondria, where it activated apoptosis. The regions that mediated 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 protein segments could be the basis of future anticancer therapies in cases where the mechanism of natural cell death is not working properly,” said senior author Dr. Assaf Friedler, professor of chemistry at the Hebrew University of Jerusalem. “We have just begun to uncover the hidden potential in the interaction between these proteins. This is an important potential target for the development of anticancer drugs that will stimulate apoptosis by interfering with its regulation.”

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Hebrew University of Jerusalem