Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside.

Abstract:

:ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved the bovine carrier structure at a resolution of 2.2 A by X-ray crystallography in complex with an inhibitor, carboxyatractyloside. Six alpha-helices form a compact transmembrane domain, which, at the surface towards the space between inner and outer mitochondrial membranes, reveals a deep depression. At its bottom, a hexapeptide carrying the signature of nucleotide carriers (RRRMMM) is located. Our structure, together with earlier biochemical results, suggests that transport substrates bind to the bottom of the cavity and that translocation results from a transient transition from a 'pit' to a 'channel' conformation.

journal_name

Nature

journal_title

Nature

authors

Pebay-Peyroula E,Dahout-Gonzalez C,Kahn R,Trézéguet V,Lauquin GJ,Brandolin G

doi

10.1038/nature02056

keywords:

subject

Has Abstract

pub_date

2003-11-06 00:00:00

pages

39-44

issue

6962

eissn

0028-0836

issn

1476-4687

pii

nature02056

journal_volume

426

pub_type

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