DOI: 10.1101/471920Nov 18, 2018Paper

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

BioRxiv : the Preprint Server for Biology
Koichi TamuraYuji Sugita


ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a wide range of substrates across biological membranes, harnessing free energy from the binding and hydrolysis of ATP. To understand the mechanism of the inward- to outward-facing transition that could be achieved by tight regulation of ATPase activity through extensive conformational changes of the protein, we applied template-based iterative all-atom molecular dynamics (MD) simulation to the heme ABC transporter BhuUV-T. The simulations, together with biased MDs, predict two new conformations of the protein, namely, occluded (Occ) and outward-facing (OF) conformations. The comparison between the inward-facing crystal structure and the predicted two structures shows atomic details of the gating motions at the transmembrane helices and dimerization of the nucleotide-binding domains (NBDs). The MD simulations further reveal a novel role of the ABC signature motifs (LSGG[Q/E]) at the NBDs in decelerating ATPase activity in the Occ form through sporadic flipping of the side chains of the LSGG[Q/E] catalytic serine residues. The orientational changes are coupled to loose NBD dimerization in the Occ state, whereas they are blocked in the OF form ...Continue Reading

Related Concepts

Adenosine Triphosphate
Integral Membrane Proteins
Heme-binding protein
ATP-Binding Cassette Transporters
Crystal Structure
Membrane Transport Proteins
Molecular Dynamics

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