Cited by 12Force Microscopy Techniques and ApplicationsProtein Structure and DynamicsDrug Transport and Resistance Mechanisms

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Probing the stability and interdomain interactions in the ABC transporter OpuA using single-molecule optical tweezers

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Abstract

Transmembrane transporter proteins are essential for maintaining cellular homeostasis and, as such, are key drug targets. Many transmembrane transporter proteins are known to undergo large structural rearrangements during their functional cycles. Despite the wealth of detailed structural and functional data available for these systems, our understanding of their dynamics and, consequently, how they function is generally limited. We introduce an innovative approach that enables us to directly measure the dynamics and stability of interdomain interactions of transmembrane proteins using optical tweezers. Focusing on the osmoregulatory ATP-binding cassette transporter OpuA from Lactococcus lactis, we examine the mechanical properties and potential interactions of its substrate-binding domains. Our measurements are performed in lipid nanodiscs, providing a native-mimicking environment for the transmembrane protein. The technique provides high spatial and temporal resolution and allows us to study the functionally relevant motions and interdomain interactions of individual transmembrane transporter proteins in real time in a lipid bilayer.

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Research works printed but not linked: 57

  1. Bustamante, 2021, Optical tweezers in single-molecule biophysics, Nat. Rev. Methods Primers, 1, 25, 10.1038/s43586-021-00021-6 · DOI
  2. Zaltron, 2020, Optical tweezers in single-molecule experiments, Eur. Phys. J. Plus, 135, 896, 10.1140/epjp/s13360-020-00907-6 · DOI
  3. Bustamante, 2020, Single-Molecule Studies of Protein Folding with Optical Tweezers, Annu. Rev. Biochem., 89, 443, 10.1146/annurev-biochem-013118-111442 · DOI
  4. Petrosyan, 2021, Single-Molecule Force Spectroscopy of Protein Folding, J. Mol. Biol., 433, 10.1016/j.jmb.2021.167207 · DOI
  5. Yu, 2012, Direct observation of multiple misfolding pathways in a single prion protein molecule, Proc. Natl. Acad. Sci. USA, 109, 5283, 10.1073/pnas.1107736109 · DOI
  6. Shank, 2010, The folding cooperativity of a protein is controlled by its chain topology, Nature, 465, 637, 10.1038/nature09021 · DOI
  7. Cecconi, 2005, Direct Observation of the Three-State Folding of a Single Protein Molecule, Science, 309, 2057, 10.1126/science.1116702 · DOI
  8. Foroutannejad, 2023, The cofactor-dependent folding mechanism of Drosophila cryptochrome revealed by single-molecule pulling experiments, Nat. Commun., 14, 1057, 10.1038/s41467-023-36701-y · DOI
  9. Pelz, 2016, Subnanometre enzyme mechanics probed by single-molecule force spectroscopy, Nat. Commun., 7, 10.1038/ncomms10848 · DOI
  10. Jahn, 2018, Folding and Domain Interactions of Three Orthologs of Hsp90 Studied by Single-Molecule Force Spectroscopy, Structure, 26, 96, 10.1016/j.str.2017.11.023 · DOI
  11. Jahn, 2014, The charged linker of the molecular chaperone Hsp90 modulates domain contacts and biological function, Proc. Natl. Acad. Sci. USA, 111, 17881, 10.1073/pnas.1414073111 · DOI
  12. Min, 2018, Unfolding of a ClC chloride transporter retains memory of its evolutionary history, Nat. Chem. Biol., 14, 489, 10.1038/s41589-018-0025-4 · DOI
  13. Kim, 2023, Robust membrane protein tweezers reveal the folding speed limit of helical membrane proteins, Elife, 12, 10.7554/eLife.85882 · DOI
  14. Wijesinghe, 2023, Single-Molecule Force Spectroscopy of Membrane Protein Folding, J. Mol. Biol., 435, 10.1016/j.jmb.2023.167975 · DOI
  15. Whited, 2014, Atomic force microscopy: A multifaceted tool to study membrane proteins and their interactions with ligands, Biochim. Biophys. Acta, 1838, 56, 10.1016/j.bbamem.2013.04.011 · DOI
  16. Ford, 2019, Learning the ABCs one at a time: Structure and mechanism of ABC transporters, Biochem. Soc. Trans., 47, 23, 10.1042/BST20180147 · DOI
  17. ter Beek, 2014, Structural diversity of ABC transporters, J. Gen. Physiol., 143, 419, 10.1085/jgp.201411164 · DOI
  18. van der Heide, 2002, ABC transporters: one, two or four extracytoplasmic substrate-binding sites?, EMBO Rep., 3, 938, 10.1093/embo-reports/kvf201 · DOI
  19. Higgins, 1981, Two periplasmic transport proteins which interact with a common membrane receptor show extensive homology: complete nucleotide sequences, Proc. Natl. Acad. Sci. USA, 78, 6038, 10.1073/pnas.78.10.6038 · DOI
  20. Schuurman-Wolters, 2005, Substrate specificity and ionic regulation of GlnPQ from Lactococcus lactis: An ATP-binding cassette transporter with four extracytoplasmic substrate-binding domains, J. Biol. Chem., 280, 23785, 10.1074/jbc.M500522200 · DOI
  21. van den Noort, 2023, The substrate-binding domains of the osmoregulatory ABC importer OpuA physically interact, Elife, 12
  22. Biemans-Oldehinkel, 2003, On the role of the two extracytoplasmic substrate-binding domains in the ABC transporter OpuA, EMBO J., 22, 5983, 10.1093/emboj/cdg581 · DOI
  23. Wood, 2001, Osmosensing and osmoregulatory compatible solute accumulation by bacteria, Comp. Biochem. Physiol. Mol. Integr. Physiol., 130, 437, 10.1016/S1095-6433(01)00442-1 · DOI
  24. Wood, 2011, Bacterial osmoregulation: A paradigm for the study of cellular homeostasis, Annu. Rev. Microbiol., 65, 215, 10.1146/annurev-micro-090110-102815 · DOI · Paper page
  25. Biemans-Oldehinkel, 2006, ABC transporter architecture and regulatory roles of accessory domains, FEBS Lett., 580, 1023, 10.1016/j.febslet.2005.11.079 · DOI
  26. Biemans-Oldehinkel, 2006, A sensor for intracellular ionic strength, Proc. Natl. Acad. Sci. USA, 103, 10624, 10.1073/pnas.0603871103 · DOI
  27. Sikkema, 2020, Gating by ionic strength and safety check by cyclic-di-AMP in the ABC transporter OpuA, Sci. Adv., 6, 10.1126/sciadv.abd7697 · DOI
  28. Wolters, 2010, Ligand binding and crystal structures of the substrate- binding domain of the ABC transporter OpuA, PLoS One, 5, 10.1371/journal.pone.0010361 · DOI
  29. Patzlaff, 2003, The ATP/substrate stoichiometry of the ATP-binding cassette (ABC) transporter OpuA, J. Biol. Chem., 278, 29546, 10.1074/jbc.M304796200 · DOI
  30. Karasawa, 2013, Physicochemical Factors Controlling the Activity and Energy Coupling of an Ionic Strength-gated ATP-binding Cassette (ABC) Transporter, J. Biol. Chem., 288, 29862, 10.1074/jbc.M113.499327 · DOI
  31. Mahmood, 2006, Ion specificity and ionic strength dependence of the osmoregulatory ABC transporter OpuA, J. Biol. Chem., 281, 29830, 10.1074/jbc.M604907200 · DOI
  32. Van Der Heide, 2000, Osmoregulated ABC-transport system of Lactococcus lactis senses water stress via changes in the physical state of the membrane, Proc. Natl. Acad. Sci. USA, 97, 7102, 10.1073/pnas.97.13.7102 · DOI
  33. van der Heide, 2001, On the osmotic signal and osmosensing mechanism of an ABC transport system for glycine betaine, EMBO J., 20, 7022, 10.1093/emboj/20.24.7022 · DOI
  34. Bayburt, 2010, Membrane protein assembly into Nanodiscs, FEBS Lett., 584, 1721, 10.1016/j.febslet.2009.10.024 · DOI
  35. Hilton, 2022, Single-molecule investigations of single-chain cellulose biosynthesis, Proc. Natl. Acad. Sci. USA, 119, 10.1073/pnas.2122770119 · DOI
  36. Crampton, 2010, Unravelling the design principles for single protein mechanical strength, Curr. Opin. Struct. Biol., 20, 508, 10.1016/j.sbi.2010.05.005 · DOI
  37. Renn, 2019, Mechanical unfolding of spectrin reveals a super-exponential dependence of unfolding rate on force, Sci. Rep., 9, 10.1038/s41598-019-46525-w · DOI
  38. Sheridan, 2019, How Fast Is Too Fast in Force-Probe Molecular Dynamics Simulations?, J. Phys. Chem. B, 123, 3658, 10.1021/acs.jpcb.9b01251 · DOI
  39. Mazal, 2018, Effect of ligand binding on a protein with a complex folding landscape, Phys. Chem. Chem. Phys., 20, 3054, 10.1039/C7CP03327C · DOI
  40. Bertz, 2009, Ligand Binding Mechanics of Maltose Binding Protein, J. Mol. Biol., 393, 1097, 10.1016/j.jmb.2009.08.066 · DOI
  41. Bauer, 2015, Nucleotides regulate the mechanical hierarchy between subdomains of the nucleotide binding domain of the Hsp70 chaperone DnaK, Proc. Natl. Acad. Sci. USA, 112, 10389, 10.1073/pnas.1504625112 · DOI
  42. Girstmair, 2019, The Hsp90 isoforms from S. cerevisiae differ in structure, function and client range, Nat. Commun., 10, 10.1038/s41467-019-11518-w · DOI
  43. Street, 2006, A molecular mechanism for osmolyte-induced protein stability, Proc. Natl. Acad. Sci. USA, 103, 13997, 10.1073/pnas.0606236103 · DOI
  44. Auton, 2011, Osmolyte effects on protein stability and solubility: A balancing act between backbone and side-chains, Biophys. Chem., 159, 90, 10.1016/j.bpc.2011.05.012 · DOI
  45. Ritchie, 2009, Reconstitution of Membrane Proteins in Phospholipid Bilayer Nanodiscs, Methods Enzymol., 464, 211, 10.1016/S0076-6879(09)64011-8 · DOI
  46. Florin, 1998, Photonic force microscope calibration by thermal noise analysis, Appl. Phys. Mater. Sci. Process, 66, S75, 10.1007/s003390051103 · DOI
  47. Abraham, 2015, Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX, 1–2, 19, 10.1016/j.softx.2015.06.001 · DOI · Paper page
  48. Best, 2012, Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ1 and χ2 Dihedral Angles, J. Chem. Theor. Comput., 8, 3257, 10.1021/ct300400x · DOI
  49. Hess, 2008, P-LINCS: A parallel linear constraint solver for molecular simulation, J. Chem. Theor. Comput., 4, 116, 10.1021/ct700200b · DOI
  50. Bussi, 2007, Canonical sampling through velocity rescaling, J. Chem. Phys., 126
  51. Parrinello, 1981, Polymorphic transitions in single crystals: A new molecular dynamics method, J. Appl. Phys., 52, 7182, 10.1063/1.328693 · DOI
  52. Darden, 1993, Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems, J. Chem. Phys., 98, 10089, 10.1063/1.464397 · DOI
  53. Mirdita, 2022, ColabFold: making protein folding accessible to all, Nat. Methods, 19, 679, 10.1038/s41592-022-01488-1 · DOI · Paper page
  54. Wenner, 2002, Salt dependence of the elasticity and overstretching transition of single DNA molecules, Biophys. J., 82, 3160, 10.1016/S0006-3495(02)75658-0 · DOI
  55. Franz, 2020, Advances in molecular simulations of protein mechanical properties and function, Curr. Opin. Struct. Biol., 61, 132, 10.1016/j.sbi.2019.12.015 · DOI
  56. Zhuang, 2022, Implementation of Telescoping Boxes in Adaptive Steered Molecular Dynamics, J. Chem. Theor. Comput., 18, 4649, 10.1021/acs.jctc.2c00498 · DOI
  57. Virtanen, 2020, SciPy 1.0: fundamental algorithms for scientific computing in Python, Nat. Methods, 17, 261, 10.1038/s41592-019-0686-2 · DOI · Paper page

Metadata

Authors
van der Sleen, L., Stevens, J. A., Marrink, S. J., Poolman, B., & Tych, K.
Affiliations
University of Groningen (NL)
Corresponding author
Poolman, Bert
Venue
Cell Reports
Publisher
Elsevier BV
Published
2024-04
Volume
43
Issue
4
Pages
114110
ISSN
2211-1247 (ISSN-L)
OpenAlex
W4394728395
Cited by
12
References
2
Citations by year
2026: 5 · 2025: 5 · 2024: 1
FWCI
1.75
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
NWO (OCENW.KLEIN.526)
Topics
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
OpuA, ABC transporters, domain-domain interactions, protein stability, substrate-binding domain, osmoregulation, Lactococcus lactis, lipid nanodiscs, single-molecule force spectroscopy, optical tweezers, protein mechanical properties
MeSH terms
Protein Domains, Single Molecule Imaging, Bacterial Proteins, Lipid Bilayers, Protein Binding, Lactococcus lactis, ATP-Binding Cassette Transporters, Optical Tweezers, Protein Stability

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