The Addressing Fragment of Mitogaligin: First Insights into Functional and Structural Properties

• Published in: Chembiochem : a European journal of chemical biology Vol. 14; no. 6; pp. 711 - 720
• Main Authors: Senille, Violette, Lelievre, Dominique, Paquet, Françoise, Garnier, Norbert, Lamb, Ned, Legrand, Alain, Delmas, Agnès F., Landon, Céline
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 15-04-2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Amino Acid Sequence; Apoptosis; Biochemistry, Molecular Biology; Blood Proteins - chemistry; Blood Proteins - metabolism; Cell Line, Tumor; Cell Survival; Cells; Cells, Cultured; coarse-grained simulation; cytotoxic peptides; Cytotoxins - chemistry; Cytotoxins - metabolism; Fibroblasts - cytology; Fibroblasts - metabolism; Galectins - chemistry; Galectins - metabolism; Humans; Life Sciences; Medical research; micelles; Mitochondria - metabolism; Models, Molecular; Molecular Sequence Data; NMR structures; Peptides; Proteins; Sequence Alignment
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201200715

Mitogaligin is a mitochondrion‐targeting protein involved in cell death. The sequence of the protein is unrelated to that of any known pro‐ or antiapoptotic protein. Mitochondrial targeting is controlled by an internal sequence from residues 31 to 53, and although this sequence is essential and sufficient to provoke cell death, the precise mechanism of action at the mitochondrial membrane remains to be elucidated. Here, by focusing on the [31–53] fragment, we first assessed and confirmed its cell cytotoxicity by microinjection. Subsequently, with the aid of membrane models, we evaluated the impact of the membrane environment on the 3D structure of the peptide and on how the peptide is embedded and oriented within membranes. The fragment is well organized, even though it does not contain a canonical secondary structure, and adopts an interfacial location. Structural comparison with other membrane‐interacting Trp‐rich peptides demonstrated similarities with the antimicrobial peptide tritrpcidin.
Mitochondrion targeting: The mitochondrial addressing fragment of mitogaligin adopts an interfacial location in membrane models, with tryptophan and leucine residues pointing towards the interior of the membrane and arginine remaining accessible to the water side. This fragment displays a high cell death induction potency when microinjected into the cytoplasm.