Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 54, Issue 8, Pages 2436-2441Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201408417
Keywords
conformation analysis; DNA; membranes; NMR spectroscopy; nucleotides
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Funding
- NIH [GM094608]
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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.
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