Rapid Enrichment of a Native Multipass Transmembrane Protein via Cell Membrane Electrophoresis through Buffer pH and Ionic Strength Adjustment.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Author(s): Liu TT;Liu TT; Huang SH; Huang SH; Chao L; Chao L
  • Source:
    Journal of the American Chemical Society [J Am Chem Soc] 2024 May 01; Vol. 146 (17), pp. 11634-11647. Date of Electronic Publication: 2024 Apr 17.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : American Chemical Society
      Original Publication: Easton, Pa. [etc.]
    • Subject Terms:
    • Abstract:
      Supported membrane electrophoresis is a promising technique for collecting membrane proteins in native bilayer environments. However, the slow mobility of typical transmembrane proteins has impeded the technique's advancement. Here, we successfully applied cell membrane electrophoresis to rapidly enrich a 12-transmembrane helix protein, glucose transporter 1 with antibodies (GLUT1 complex), by tuning the buffer pH and ionic strength. The identified conditions allowed the separation of the GLUT1 complex and a lipid probe, Fast-DiO, within a native-like environment in a few minutes. A force model was developed to account for distinct electric and drag forces acting on the transmembrane and aqueous-exposed portion of a transmembrane protein as well as the electroosmotic force. This model not only elucidates the impact of size and charge properties of transmembrane proteins but also highlights the influence of pH and ionic strength on the driving forces and, consequently, electrophoretic mobility. Model predictions align well with experimentally measured electrophoretic mobilities of the GLUT1 complex and Fast-DiO at various pH and ionic strengths as well as with several lipid probes, lipid-anchored proteins, and reconstituted membrane proteins from previous studies. Force analyses revealed the substantial membrane drag of the GLUT1 complex, significantly slowing down electrophoretic mobility. Besides, the counterbalance of similar magnitudes of electroosmotic and electric forces results in a small net driving force and, consequently, reduced mobility under typical neutral pH conditions. Our results further highlight how the size and charge properties of transmembrane proteins influence the suitable range of operating conditions for effective movement, providing potential applications for concentrating and isolating membrane proteins within this platform.
    • References:
      Arch Biochem Biophys. 1968 Oct;128(1):51-69. (PMID: 4300292)
      Biochim Biophys Acta. 2004 Nov 3;1666(1-2):62-87. (PMID: 15519309)
      Antibodies (Basel). 2019 Mar 14;8(1):. (PMID: 31544830)
      Nature. 2009 May 21;459(7245):379-85. (PMID: 19458714)
      Langmuir. 2018 Jan 23;34(3):1061-1072. (PMID: 29020444)
      Biophys J. 2023 May 2;122(9):1720-1731. (PMID: 37020419)
      Nat Rev Drug Discov. 2006 Dec;5(12):993-6. (PMID: 17139284)
      Anal Chem. 2013 Jun 18;85(12):6047-52. (PMID: 23731179)
      Nucleic Acids Res. 2021 Jan 8;49(D1):D480-D489. (PMID: 33237286)
      Electrophoresis. 2016 Mar;37(5-6):762-8. (PMID: 26773565)
      Langmuir. 2007 May 8;23(10):5638-44. (PMID: 17408291)
      Protein Sci. 2014 Jun;23(6):769-89. (PMID: 24652590)
      Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5083-7. (PMID: 24706877)
      J Am Chem Soc. 2005 Oct 19;127(41):14383-7. (PMID: 16218633)
      Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2098-102. (PMID: 16461891)
      Biophys J. 1996 Nov;71(5):2716-23. (PMID: 8913608)
      Biophys J. 1981 Apr;34(1):85-93. (PMID: 6894257)
      Biophys J. 2006 Oct 1;91(7):2393-8. (PMID: 16829562)
      J Am Chem Soc. 2014 Jan 8;136(1):100-3. (PMID: 24345193)
      Electrophoresis. 2008 Mar;29(5):994-1005. (PMID: 18271065)
      Langmuir. 2006 Feb 28;22(5):2384-91. (PMID: 16489833)
      Biochim Biophys Acta. 1982 Nov 8;692(2):278-86. (PMID: 7171596)
      Chem Commun (Camb). 2017 Apr 11;53(30):4250-4253. (PMID: 28361139)
      Anal Chem. 2011 Oct 15;83(20):7876-80. (PMID: 21958061)
      Electrophoresis. 1995 Aug;16(8):1377-80. (PMID: 8529600)
      Soft Matter. 2016 Aug 17;12(33):6954-63. (PMID: 27476605)
      Biophys J. 1992 Nov;63(5):1346-54. (PMID: 19431856)
      J Am Chem Soc. 2011 May 4;133(17):6521-4. (PMID: 21476549)
      Annu Rev Biophys Biomol Struct. 2007;36:107-30. (PMID: 17263662)
      Fundam Clin Pharmacol. 2008 Dec;22(6):615-21. (PMID: 19049666)
      Biophys J. 1995 Nov;69(5):1972-5. (PMID: 8580340)
      Biochim Biophys Acta. 2014 Mar;1838(3):802-13. (PMID: 24600711)
      Integr Biol (Camb). 2009 Feb;1(2):205-11. (PMID: 20023804)
      Langmuir. 2013 Jun 11;29(23):6953-63. (PMID: 23683055)
      J Am Chem Soc. 2007 Jul 4;129(26):8072-3. (PMID: 17564451)
      Crystals (Basel). 2020 Feb;10(2):. (PMID: 32494365)
      Anal Chem. 2011 Mar 15;83(6):2090-6. (PMID: 21319743)
      Nature. 2003 Mar 6;422(6927):37-44. (PMID: 12621426)
      Nat Rev Neurosci. 2007 Feb;8(2):128-40. (PMID: 17195035)
      Anal Chem. 2013 Nov 19;85(22):10803-11. (PMID: 24191728)
      Electrophoresis. 2002 Feb;23(4):613-20. (PMID: 11870773)
      J Am Chem Soc. 2009 Apr 15;131(14):5294-7. (PMID: 19309139)
      Biophys J. 2013 Jul 16;105(2):455-62. (PMID: 23870266)
      Langmuir. 2011 Feb 15;27(4):1430-9. (PMID: 21142022)
      Langmuir. 2016 Mar 29;32(12):2963-74. (PMID: 26812542)
      Sci Rep. 2019 Feb 26;9(1):2747. (PMID: 30808885)
    • Accession Number:
      0 (Membrane Proteins)
      0 (Buffers)
      0 (Glucose Transporter Type 1)
    • Publication Date:
      Date Created: 20240417 Date Completed: 20240501 Latest Revision: 20240505
    • Publication Date:
      20240505
    • Accession Number:
      PMC11066866
    • Accession Number:
      10.1021/jacs.3c13579
    • Accession Number:
      38628144