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Mapping Conformational Heterogeneity of Mitochondrial Nucleotide Transporter in Uninhibited States
Author(s) -
Sounier Remy,
Bellot Gaetan,
Chou James J.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201408417
Subject(s) - residual dipolar coupling , transporter , chemistry , biophysics , nucleotide , conformational change , transmembrane domain , inner mitochondrial membrane , transmembrane protein , crystallography , nuclear magnetic resonance spectroscopy , stereochemistry , membrane , biochemistry , biology , receptor , gene
One of the less well understood aspects of membrane transporters is the dynamic coupling between conformational change and substrate transport. NMR approaches are used herein to investigate conformational heterogeneity of the GTP/GDP carrier (GGC) from yeast mitochondria. NMR residual dipolar coupling (RDC) analysis of GGC in a DNA‐origami nanotube liquid crystal shows that several structured segments have different generalized degrees of order (GDO), thus indicating the presence of conformational heterogeneity. Complete GDO mapping reveals asymmetry between domains of the transporter and even within certain transmembrane helices. Nucleotide binding partially reduces local structural heterogeneity, and the substrate binds to multiple sites along the transport cavity. These observations suggest that mitochondrial carriers in the uninhibited states are intrinsically plastic and structural plasticity is asymmetrically distributed among the three homologous domains.