Medical College of Wisconsin
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Mapping the specific cytoprotective interaction of humanin with the pro-apoptotic protein bid. Chem Biol Drug Des 2007 Nov;70(5):383-92

Date

10/12/2007

Pubmed ID

17927731

Pubmed Central ID

PMC2917600

DOI

10.1111/j.1747-0285.2007.00576.x

Scopus ID

2-s2.0-35348952538 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Humanin is a short endogenous peptide, which can provide protection from cell death through its association with various receptors, including the pro-apoptotic Bcl-2 family proteins Bid, Bim, and Bax. By using NMR chemical shift mapping experiments, we demonstrate that the interaction between Humanin-derived peptides and Bid is specific, and we localize the binding site to a region on the surface of Bid, which includes residues from the conserved helical BH3 domain of the protein. The BH3 domain mediates the association of Bid with other Bcl-2 family members and is essential for the protein's cytotoxic activity. The data suggest that Humanin exerts its cytoprotective activity by engaging the Bid BH3 domain; this would hinder the association of Bid with other Bcl-2 family proteins, thereby mitigating its toxicity. The identification of a Humanin-specific binding site on the surface of Bid reinforces its importance as a direct modulator of programmed cell death, and suggests a strategy for the design of cytoprotective peptide inhibitors of Bid.

Author List

Choi J, Zhai D, Zhou X, Satterthwait A, Reed JC, Marassi FM

Author

Francesca M. Marassi PhD Chair, Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Apoptosis
Apoptosis Regulatory Proteins
BH3 Interacting Domain Death Agonist Protein
Bcl-2-Like Protein 11
Cell Death
Conserved Sequence
Humans
Intracellular Signaling Peptides and Proteins
Magnetic Resonance Spectroscopy
Membrane Proteins
Mice
Models, Molecular
Molecular Sequence Data
Protein Conformation
Proto-Oncogene Proteins
Sequence Alignment
Sequence Homology, Amino Acid
bcl-2-Associated X Protein