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Study of Conformational Transition of a Protein Secretion ABC Transporter using Molecular Dynamic
Journal article   Open access   Peer reviewed

Study of Conformational Transition of a Protein Secretion ABC Transporter using Molecular Dynamic

Ahmad Raeisi Najafi, Reza Dastvan, Hassane S. Mchaourab and Emad Tajkhorshid
Biophysical journal, v 114(3), pp 148a-149a
02 Feb 2018
DOI: https://doi.org/10.1016/j.bpj.2017.11.833
url
https://doi.org/10.1016/j.bpj.2017.11.833View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Among the various ABC transporters, those involved in protein secretion have a unique structure in addition to the transmembrane (TMDs) and nucleotide-binding (NBDs) domains which are common in all ABC transporters. This family of transporters, known as the peptidase-containing ABC transporters (PCATs), contain additional peptidase domains (PEPs), the main function of which is processing of polypeptide substrates. In this study, we use molecular dynamics (MD) simulations to characterize and compare the dynamics of PCAT1 in the absence and presence of ATP. Using the simulations, we monitor the separation of the NBDs, TMDs, and PEPs to capture the conformational response of PCAT1 to ATP binding. We also aim to characterize the alternate conformation of PCAT1 formed during the transport cycle using non-equilibrium MD simulations. To investigate the conformational changes, we consider three states: an IF model (unknown), an occluded state, and an outward-facing (OF) model (unknown). The IF state is constructed based on the semi-open state of PCAT1 (PDB code 4RY2) while the OF state is rebuilt using a homology model based on a structural template from the OF state of the bacterial ABC transporter MsbA (PDB code 3B60). ATP molecules and Mg+2 are docked into the NBDs of the OF state based on the crystal structure of the structure Mg-ATP-bound NBD of the of HlyB (PDB code 1XEF). To characterize the functional properties of the PEPs, we perform non-equilibrium MD simulations from the IF state to the OF state in the full-length protein as well as after removing the peptidase domains. These fully atomistic models along with non-equilibrium MD simulations employing different sets of collective variables reveal structural elements and changes underlying the alternating access mechanism in this bacterial protein exporter.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biophysics
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