[1] |
Thomas C, Tampé R. Structural and mechanistic principles of ABC transporters. Annu. Rev. Biochem., 2020, 89: 605–636. doi: 10.1146/annurev-biochem-011520-105201
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[2] |
Srikant S, Gaudet R. Mechanics and pharmacology of substrate selection and transport by eukaryotic ABC exporters. Nat. Struct. Mol. Biol., 2019, 26 (9): 792–801. doi: 10.1038/s41594-019-0280-4
|
[3] |
Hofmann S, Januliene D, Mehdipour A R, et al. Conformation space of a heterodimeric ABC exporter under turnover conditions. Nature, 2019, 571 (7766): 580–583. doi: 10.1038/s41586-019-1391-0
|
[4] |
Locher K P. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat. Struct. Mol. Biol., 2016, 23 (6): 487–493. doi: 10.1038/nsmb.3216
|
[5] |
Robey R W, Pluchino K M, Hall M D, et al. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat. Rev. Cancer, 2018, 18 (7): 452–464. doi: 10.1038/s41568-018-0005-8
|
[6] |
Dawson R J P, Locher K P. Structure of a bacterial multidrug ABC transporter. Nature, 2006, 443 (7108): 180–185. doi: 10.1038/nature05155
|
[7] |
Dawson R J P, Locher K P. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett., 2007, 581 (5): 935–938. doi: 10.1016/j.febslet.2007.01.073
|
[8] |
Ward A, Reyes C L, Yu J, et al. Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc. Natl. Acad. Sci. U.S.A., 2007, 104 (48): 19005–19010. doi: 10.1073/pnas.0709388104
|
[9] |
Mi W, Li Y, Yoon S H, et al. Structural basis of MsbA-mediated lipopolysaccharide transport. Nature, 2017, 549 (7671): 233–237. doi: 10.1038/nature23649
|
[10] |
Ho H, Miu A, Alexander M K, et al. Structural basis for dual-mode inhibition of the ABC transporter MsbA. Nature, 2018, 557 (7704): 196–201. doi: 10.1038/s41586-018-0083-5
|
[11] |
Padayatti P S, Lee S C, Stanfield R L, et al. Structural insights into the lipid A transport pathway in MsbA. Structure, 2019, 27 (7): 1114–1123.e3. doi: 10.1016/j.str.2019.04.007
|
[12] |
Angiulli G, Dhupar H S, Suzuki H, et al. New approach for membrane protein reconstitution into peptidiscs and basis for their adaptability to different proteins. eLife, 2020, 9: e53530. doi: 10.7554/eLife.53530
|
[13] |
Thélot F A, Zhang W, Song K, et al. Distinct allosteric mechanisms of first-generation MsbA inhibitors. Science, 2021, 374 (6567): 580–585. doi: 10.1126/science.abi9009
|
[14] |
Moradi M, Tajkhorshid E. Mechanistic picture for conformational transition of a membrane transporter at atomic resolution. Proc. Natl. Acad. Sci. U.S.A., 2013, 110 (47): 18916–18921. doi: 10.1073/pnas.1313202110
|
[15] |
Wang Z, Liao J L. Probing structural determinants of ATP-binding cassette exporter conformational transition using coarse-grained molecular dynamics. J. Phys. Chem. B, 2015, 119 (4): 1295–1301. doi: 10.1021/jp509178k
|
[16] |
Kieuvongngam V, Chen J. Structures of the peptidase-containing ABC transporter PCAT1 under equilibrium and nonequilibrium conditions. Proc. Natl. Acad. Sci. U.S.A., 2022, 119 (4): e2120534119. doi: 10.1073/pnas.2120534119
|
[17] |
Abraham M J, Murtola T, Schulz R, et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 2015, 1–2: 19–25. doi: 10.1016/j.softx.2015.06.001
|
[18] |
Simpson B W, Trent M S. Pushing the envelope: LPS modifications and their consequences. Nat. Rev. Microbiol., 2019, 17 (7): 403–416. doi: 10.1038/s41579-019-0201-x
|
[19] |
Marrink S J, Risselada H J, Yefimov S, et al. The MARTINI force field: Coarse grained model for biomolecular simulations. J. Phys. Chem. B, 2007, 111 (27): 7812–7824. doi: 10.1021/jp071097f
|
[20] |
Monticelli L, Kandasamy S K, Periole X, et al. The MARTINI coarse-grained force field: Extension to proteins. J. Chem. Theory Comput., 2008, 4 (5): 819–834. doi: 10.1021/ct700324x
|
[21] |
López C A, Sovova Z, van Eerden F J, et al. Martini force field parameters for glycolipids. J. Chem. Theory Comput., 2013, 9 (3): 1694–1708. doi: 10.1021/ct3009655
|
[22] |
Darden T, York D, Pedersen L. Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems. J. Chem. Phys., 1993, 98: 10089–10092. doi: 10.1063/1.464397
|
[23] |
Huang Y, Xu H C, Liao J L. Coarse-grained free-energy simulations of conformational state transitions in an adenosine 5′-triphosphate-binding cassette exporter. Chin. J. Chem. Phys., 2020, 33: 712–716. doi: 10.1063/1674-0068/cjcp1908149
|
[24] |
Periole X, Knepp A M, Sakmar T P, et al. Structural determinants of the supramolecular organization of G protein-coupled receptors in bilayers. J. Am. Chem. Soc., 2012, 134 (26): 10959–10965. doi: 10.1021/ja303286e
|
[25] |
Lemkul J A, Bevan D R. Assessing the stability of Alzheimer’s amyloid protofibrils using molecular dynamics. J. Phys. Chem. B, 2010, 114 (4): 1652–1660. doi: 10.1021/jp9110794
|
[26] |
Jakubec D, Vondrášek J. Efficient estimation of absolute binding free energy for a homeodomain-DNA complex from nonequilibrium pulling simulations. J. Chem. Theory Comput., 2020, 16 (4): 2034–2041. doi: 10.1021/acs.jctc.0c00006
|
[27] |
Xing X, Liu C, Ali A, et al. Novel disassembly mechanisms of sigmoid Aβ42 protofibrils by introduced neutral and charged drug molecules. ACS Chem. Neuro., 2020, 11 (1): 45–56. doi: 10.1021/acschemneuro.9b00550
|
[28] |
Wassenaar T A, Pluhackova K, Böckmann R A, et al. Going backward: A flexible geometric approach to reverse transformation from coarse grained to atomistic models. J. Chem. Theory Comput., 2014, 10 (2): 676–690. doi: 10.1021/ct400617g
|
[29] |
Hohl M, Briand C, Grütter M G, et al. Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. Nat. Struct. Mol. Biol., 2012, 19 (4): 395–402. doi: 10.1038/nsmb.2267
|
[30] |
Jin M S, Oldham M L, Zhang Q, et al. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature, 2012, 490 (7421): 566–569. doi: 10.1038/nature11448
|
[31] |
Huang W, Liao J L. Catalytic mechanism of the maltose transporter hydrolyzing ATP. Biochemistry, 2016, 55 (1): 224–231. doi: 10.1021/acs.biochem.5b00970
|
JUSTC-2022-0134 Supporting information.docx |
Figure 1. Three conformations of an ABC exporter. (a) Inward-facing (IF) conformation, in which the internal gate is open whereas the external gate is closed. (b) Occluded (OC) conformation, in which both the internal and external gates are closed. (c) Outward-facing (OF) conformation, in which the internal gate is closed whereas the external gate is open. The TMD helices, TM1−TM6 on one subunit and TM1′−TM6′ on the other, are colored red and blue, respectively. The intracellular coupling helices ICH1 (ICH1′), which links TM2 (TM2′) and TM3 (TM3′) at its N- and C-terminus, and ICH2 (ICH2′), which links TM4 (TM4′) and TM5 (TM5′), are colored green and yellow, respectively.
Figure 2. Potential of mean force (PMF) expressed as a function of the COM distances, d1, for the internal gate, and d2, for the external gate. (a) d1=2.48 nm and d2=2.83 nm, (b) d1=2.61 nm and d2=2.42 nm, (c) d1=3.21 nm and d2=2.39 nm, and (d) d1=3.48–3.82 nm and d2=2.34 nm represent the OF, OC, IF1, and IF2 states, respectively. The coarse-grained structures, which represent the (a) OF, (b) OC, (c) IF1, and (d) IF2 states, and their corresponding atomistic structures are also presented.
Figure
4.
(A) Coarse-grained structures from the CG-MD simulations for the (a) OF, (b) OC, (c) IF1, and (d) IF2 states and (B) a mechanistic model for conformational state transitions in response to NBD dissociation. For clarity, two NBDs are presented with two balls (red and blue), and only TM3 and TM4-TM5 (red) and TM3′ and TM4′-TM5′ (blue) are presented with rectangular sticks. The COM distances d1 and d2 are displayed in (A). In (B), the wider rectangular sticks represent TM4-TM5 (red, TM2′ not shown) and TM4′-TM5′ (blue, TM2 not shown), whereas the narrower rectangular sticks represent TM3 (red) and TM3′ (blue). In (B), symbols
[1] |
Thomas C, Tampé R. Structural and mechanistic principles of ABC transporters. Annu. Rev. Biochem., 2020, 89: 605–636. doi: 10.1146/annurev-biochem-011520-105201
|
[2] |
Srikant S, Gaudet R. Mechanics and pharmacology of substrate selection and transport by eukaryotic ABC exporters. Nat. Struct. Mol. Biol., 2019, 26 (9): 792–801. doi: 10.1038/s41594-019-0280-4
|
[3] |
Hofmann S, Januliene D, Mehdipour A R, et al. Conformation space of a heterodimeric ABC exporter under turnover conditions. Nature, 2019, 571 (7766): 580–583. doi: 10.1038/s41586-019-1391-0
|
[4] |
Locher K P. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat. Struct. Mol. Biol., 2016, 23 (6): 487–493. doi: 10.1038/nsmb.3216
|
[5] |
Robey R W, Pluchino K M, Hall M D, et al. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat. Rev. Cancer, 2018, 18 (7): 452–464. doi: 10.1038/s41568-018-0005-8
|
[6] |
Dawson R J P, Locher K P. Structure of a bacterial multidrug ABC transporter. Nature, 2006, 443 (7108): 180–185. doi: 10.1038/nature05155
|
[7] |
Dawson R J P, Locher K P. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett., 2007, 581 (5): 935–938. doi: 10.1016/j.febslet.2007.01.073
|
[8] |
Ward A, Reyes C L, Yu J, et al. Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc. Natl. Acad. Sci. U.S.A., 2007, 104 (48): 19005–19010. doi: 10.1073/pnas.0709388104
|
[9] |
Mi W, Li Y, Yoon S H, et al. Structural basis of MsbA-mediated lipopolysaccharide transport. Nature, 2017, 549 (7671): 233–237. doi: 10.1038/nature23649
|
[10] |
Ho H, Miu A, Alexander M K, et al. Structural basis for dual-mode inhibition of the ABC transporter MsbA. Nature, 2018, 557 (7704): 196–201. doi: 10.1038/s41586-018-0083-5
|
[11] |
Padayatti P S, Lee S C, Stanfield R L, et al. Structural insights into the lipid A transport pathway in MsbA. Structure, 2019, 27 (7): 1114–1123.e3. doi: 10.1016/j.str.2019.04.007
|
[12] |
Angiulli G, Dhupar H S, Suzuki H, et al. New approach for membrane protein reconstitution into peptidiscs and basis for their adaptability to different proteins. eLife, 2020, 9: e53530. doi: 10.7554/eLife.53530
|
[13] |
Thélot F A, Zhang W, Song K, et al. Distinct allosteric mechanisms of first-generation MsbA inhibitors. Science, 2021, 374 (6567): 580–585. doi: 10.1126/science.abi9009
|
[14] |
Moradi M, Tajkhorshid E. Mechanistic picture for conformational transition of a membrane transporter at atomic resolution. Proc. Natl. Acad. Sci. U.S.A., 2013, 110 (47): 18916–18921. doi: 10.1073/pnas.1313202110
|
[15] |
Wang Z, Liao J L. Probing structural determinants of ATP-binding cassette exporter conformational transition using coarse-grained molecular dynamics. J. Phys. Chem. B, 2015, 119 (4): 1295–1301. doi: 10.1021/jp509178k
|
[16] |
Kieuvongngam V, Chen J. Structures of the peptidase-containing ABC transporter PCAT1 under equilibrium and nonequilibrium conditions. Proc. Natl. Acad. Sci. U.S.A., 2022, 119 (4): e2120534119. doi: 10.1073/pnas.2120534119
|
[17] |
Abraham M J, Murtola T, Schulz R, et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 2015, 1–2: 19–25. doi: 10.1016/j.softx.2015.06.001
|
[18] |
Simpson B W, Trent M S. Pushing the envelope: LPS modifications and their consequences. Nat. Rev. Microbiol., 2019, 17 (7): 403–416. doi: 10.1038/s41579-019-0201-x
|
[19] |
Marrink S J, Risselada H J, Yefimov S, et al. The MARTINI force field: Coarse grained model for biomolecular simulations. J. Phys. Chem. B, 2007, 111 (27): 7812–7824. doi: 10.1021/jp071097f
|
[20] |
Monticelli L, Kandasamy S K, Periole X, et al. The MARTINI coarse-grained force field: Extension to proteins. J. Chem. Theory Comput., 2008, 4 (5): 819–834. doi: 10.1021/ct700324x
|
[21] |
López C A, Sovova Z, van Eerden F J, et al. Martini force field parameters for glycolipids. J. Chem. Theory Comput., 2013, 9 (3): 1694–1708. doi: 10.1021/ct3009655
|
[22] |
Darden T, York D, Pedersen L. Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems. J. Chem. Phys., 1993, 98: 10089–10092. doi: 10.1063/1.464397
|
[23] |
Huang Y, Xu H C, Liao J L. Coarse-grained free-energy simulations of conformational state transitions in an adenosine 5′-triphosphate-binding cassette exporter. Chin. J. Chem. Phys., 2020, 33: 712–716. doi: 10.1063/1674-0068/cjcp1908149
|
[24] |
Periole X, Knepp A M, Sakmar T P, et al. Structural determinants of the supramolecular organization of G protein-coupled receptors in bilayers. J. Am. Chem. Soc., 2012, 134 (26): 10959–10965. doi: 10.1021/ja303286e
|
[25] |
Lemkul J A, Bevan D R. Assessing the stability of Alzheimer’s amyloid protofibrils using molecular dynamics. J. Phys. Chem. B, 2010, 114 (4): 1652–1660. doi: 10.1021/jp9110794
|
[26] |
Jakubec D, Vondrášek J. Efficient estimation of absolute binding free energy for a homeodomain-DNA complex from nonequilibrium pulling simulations. J. Chem. Theory Comput., 2020, 16 (4): 2034–2041. doi: 10.1021/acs.jctc.0c00006
|
[27] |
Xing X, Liu C, Ali A, et al. Novel disassembly mechanisms of sigmoid Aβ42 protofibrils by introduced neutral and charged drug molecules. ACS Chem. Neuro., 2020, 11 (1): 45–56. doi: 10.1021/acschemneuro.9b00550
|
[28] |
Wassenaar T A, Pluhackova K, Böckmann R A, et al. Going backward: A flexible geometric approach to reverse transformation from coarse grained to atomistic models. J. Chem. Theory Comput., 2014, 10 (2): 676–690. doi: 10.1021/ct400617g
|
[29] |
Hohl M, Briand C, Grütter M G, et al. Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. Nat. Struct. Mol. Biol., 2012, 19 (4): 395–402. doi: 10.1038/nsmb.2267
|
[30] |
Jin M S, Oldham M L, Zhang Q, et al. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature, 2012, 490 (7421): 566–569. doi: 10.1038/nature11448
|
[31] |
Huang W, Liao J L. Catalytic mechanism of the maltose transporter hydrolyzing ATP. Biochemistry, 2016, 55 (1): 224–231. doi: 10.1021/acs.biochem.5b00970
|