TY - JOUR
T1 - Single-molecule probing of the conformational homogeneity of the ABC transporter BtuCD
AU - Yang, Min
AU - Livnat Levanon, Nurit
AU - Acar, Burçin
AU - Aykac Fas, Burcu
AU - Masrati, Gal
AU - Rose, Jessica
AU - Ben-Tal, Nir
AU - Haliloglu, Turkan
AU - Zhao, Yongfang
AU - Lewinson, Oded
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/7/1
Y1 - 2018/7/1
N2 - ATP-binding cassette (ABC) transporters use the energy of ATP hydrolysis to move molecules through cellular membranes. They are directly linked to human diseases, cancer multidrug resistance, and bacterial virulence. Very little is known of the conformational dynamics of ABC transporters, especially at the single-molecule level. Here, we combine single-molecule spectroscopy and a novel molecular simulation approach to investigate the conformational dynamics of the ABC transporter BtuCD. We observe a single dominant population of molecules in each step of the transport cycle and tight coupling between conformational transitions and ligand binding. We uncover transient conformational changes that allow substrate to enter the transporter. This is followed by a 'squeezing' motion propagating from the extracellular to the intracellular side of the translocation cavity. This coordinated sequence of events provides a mechanism for the unidirectional transport of vitamin B 12 by BtuCD.
AB - ATP-binding cassette (ABC) transporters use the energy of ATP hydrolysis to move molecules through cellular membranes. They are directly linked to human diseases, cancer multidrug resistance, and bacterial virulence. Very little is known of the conformational dynamics of ABC transporters, especially at the single-molecule level. Here, we combine single-molecule spectroscopy and a novel molecular simulation approach to investigate the conformational dynamics of the ABC transporter BtuCD. We observe a single dominant population of molecules in each step of the transport cycle and tight coupling between conformational transitions and ligand binding. We uncover transient conformational changes that allow substrate to enter the transporter. This is followed by a 'squeezing' motion propagating from the extracellular to the intracellular side of the translocation cavity. This coordinated sequence of events provides a mechanism for the unidirectional transport of vitamin B 12 by BtuCD.
UR - http://www.scopus.com/inward/record.url?scp=85048823546&partnerID=8YFLogxK
U2 - 10.1038/s41589-018-0088-2
DO - 10.1038/s41589-018-0088-2
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AN - SCOPUS:85048823546
SN - 1552-4450
VL - 14
SP - 715
EP - 722
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 7
ER -
