ArticleProtein science : a publication of the Protein Society2021
The crystal structure of the CmABCB1 G132V mutant, which favors the outward-facing state, reveals the mechanism of the pivotal joint between TM1 and TM3.
Article in Protein science : a publication of the Protein Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 3 citations in OpenAlex.
- Article
- Structure-based alteration of tryptophan residues of the multidrug transporter CmABCB1 to assess substrate binding using fluorescence spectroscopy.Protein science : a publication of the Protein Society · 2022Article
- The crystal structure of the CmABCB1 G132V mutant, which favors the outward-facing state, reveals the mechanism of the pivotal joint between TM1 and TM3.Protein science : a publication of the Protein Society · 2021Article
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3 authors at 1 institution in 1 country.
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Abstract
CmABCB1 is a homologue of human P-glycoprotein, which extrudes various substrates by iterative cycles of conformational changes between the inward- and outward-facing states. Comparison of the inward- and outward-facing structures of CmABCB1 suggested that pivotal joints in the transmembrane domain regulate the tilt of transmembrane helices. Transmembrane helix 1 (TM1) forms a tight helix-helix contact with TM3 at the TM1-3 joint. Mutation of Gly132 to valine at the TM1-3 joint, G132V, caused a 10-fold increase in ATPase activity, but the mechanism underlying this change remains unclear. Here, we report a crystal structure of the outward-facing state of the CmABCB1 G132V mutant at a 2.15 Å resolution. We observed structural displacements between the outward-facing states of G132V and the previous one at the region around the TM1-3 joint, and a significant expansion at the extracellular gate. We hypothesize that steric hindrance caused by the Val substitution shifted the conformational equilibrium toward the outward-facing state, favoring the dimeric state of the nucleotide-binding domains and thereby increasing the ATPase activity of the G132V mutant.
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