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Membrane protein frustration: protein incorporation into hydrophobic mismatched binary lipid mixtures

David Stopar1, Ruud B Spruijt, Marcus A Hemminga

  • 1University of Ljubljana, Biotechnical Faculty, Ljubljana, Slovenia.

Biophysical Journal
|February 17, 2009
PubMed

Insights

Bacteriophage M13 coat protein prefers shorter lipid chains (14:1PC) over longer ones (22:1PC) due to hydrophobic mismatch. This preference is evolutionarily advantageous for the M13 bacteriophage in its host, Escherichia coli.

Area of Science:

  • Biophysics
  • Structural Biology
  • Membrane Protein Biochemistry

Background:

  • Bacteriophage M13 major coat protein interacts with lipid bilayers.
  • Hydrophobic mismatch occurs when protein and lipid bilayer hydrophobic depths differ, potentially affecting protein stability and function.
  • Understanding protein-lipid interactions is crucial for membrane biology.

Purpose of the Study:

  • To investigate the interaction of M13 major coat protein with binary lipid mixtures of differing hydrophobic lengths (14:1PC and 22:1PC).
  • To determine how hydrophobic mismatch influences protein conformation and lipid preference.
  • To explore the evolutionary implications of these interactions for M13 bacteriophage.

Main Methods:

  • Circular Dichroism (CD) spectroscopy to assess protein secondary structure.
  • Site-directed spin-label electron spin resonance (ESR) spectroscopy to probe protein environment and dynamics.
  • Reconstitution of M13 major coat protein into defined lipid bilayers.

Main Results:

  • M13 coat protein maintains an alpha-helical conformation across different lipid mixtures.
  • A specific spin-labeled mutant (I39C) within the hydrophobic core senses the phase transition of 22:1PC, while another (T46C) at the interface does not.
  • The protein preferentially partitions into the shorter 14:1PC lipid bilayers, irrespective of temperature relative to the 22:1PC phase transition.

Conclusions:

  • The M13 coat protein avoids hydrophobic mismatch by preferentially associating with shorter lipid acyl chains (14:1PC).
  • Protein tilt angle and the energetic penalty of insertion into thicker 22:1PC bilayers drive this lipid preference.
  • This lipid selection mechanism is evolutionarily justified, aligning with the lipid composition of its host, Escherichia coli.

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