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

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 suff...

Full description

Saved in:

Bibliographic Details
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
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	istex:9F2C8C512274862D451AB9BDC5695ED8BA16CBA1 ark:/67375/WNG-N16SNXR6-3 CNRS Région Centre La ligue contre le cancer ArticleID:CBIC201200715
ISSN:	1439-4227 1439-7633
DOI:	10.1002/cbic.201200715