C(alpha)-trace model of the transmembrane domain of human copper transporter 1, motion and functional implications.

ABSTRACT: The trimeric human copper transporter 1 (hCTR1) is essential for copper uptake and is implicated in sensitivity to chemotherapy drugs. Using the cryoelectron microscopy (cryoEM) map of hCTR1 and evolutionary data, we constructed a Calpha-trace model of the membrane region. The model structure, supported by mutagenesis data, was used to investigate global dynamics through elastic network models. Identified as dominant hinge regions, hCTR1's MxxxM and GxxxG motifs were shown to have significant roles in functional movements characterized by the two slowest modes of motion. Both modes predicted significant changes at the wide cytoplasmic pore region; the slowest mode introduced a rotational motion around the pore central axis, whereas in the following mode the cytoplasmic parts of the helices

SUBMITTER: Schushan M 

PROVIDER: S-EPMC2890728 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature