Conformational Changes of the Antibacterial Peptide ATP Binding Cassette Transporter McjD Revealed by Molecular Dynamics Simulations

Gu, Ruo-Xu, Corradi, Valentina, Singh, Gurpreet, Choudhury, Hassanul G., Beis, Konstantinos and Tieleman, D. Peter (2015) Conformational Changes of the Antibacterial Peptide ATP Binding Cassette Transporter McjD Revealed by Molecular Dynamics Simulations. Biochemistry, 54 38: 5989-5998. doi:10.1021/acs.biochem.5b00753


Author Gu, Ruo-Xu
Corradi, Valentina
Singh, Gurpreet
Choudhury, Hassanul G.
Beis, Konstantinos
Tieleman, D. Peter
Title Conformational Changes of the Antibacterial Peptide ATP Binding Cassette Transporter McjD Revealed by Molecular Dynamics Simulations
Journal name Biochemistry   Check publisher's open access policy
ISSN 1520-4995
0006-2960
Publication date 2015-09-03
Year available 2015
Sub-type Article (original research)
DOI 10.1021/acs.biochem.5b00753
Open Access Status Not Open Access
Volume 54
Issue 38
Start page 5989
End page 5998
Total pages 10
Place of publication Washington, United States
Publisher American Chemical Society
Collection year 2016
Language eng
Formatted abstract
The ATP binding cassette (ABC) transporters form one of the largest protein superfamilies. They use the energy of ATP hydrolysis to transport chemically diverse ligands across membranes. An alternating access mechanism in which the transporter switches between inward- and outward-facing conformations has been proposed to describe the translocation process. One of the main open questions in this process is the degree of opening of the transporter at different stages of the transport cycle, as crystal structures and biochemical data have suggested a wide range of distances between nucleotide binding domains. Recently, the crystal structure of McjD, an antibacterial peptide ABC transporter from Escherichia coli, revealed a new occluded intermediate state of the transport cycle. The transmembrane domain is closed on both sides of the membrane, forming a cavity that can accommodate its ligand, MccJ25, a lasso peptide of 21 amino acids. In this work, we investigate the degree of opening of the transmembrane cavity required for ligand translocation. By means of steered molecular dynamics simulations, the ligand was pulled from the internal cavity to the extracellular side. This resulted in an outward-facing state. Comparison with existing outward-facing crystal structures shows a smaller degree of opening in the simulations, suggesting that the large conformational changes in some crystal structures may not be necessary even for a large substrate like MccJ25.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Institute for Molecular Bioscience - Publications
 
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