Premium
Bacterial Analogs to Cholesterol Affect Dimerization of Proteorhodopsin and Modulates Preferred Dimer Interface
Author(s) -
Sefah Eric,
Mertz Blake
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04031
Subject(s) - hopanoids , membrane , dimer , biophysics , chemistry , monomer , molecular dynamics , cell membrane , membrane protein , crystallography , biochemistry , biology , computational chemistry , organic chemistry , paleontology , structural basin , source rock , polymer
Hopanoids, the bacterial analogs of sterols, are ubiquitous in bacteria and play a significant role in organismal survival under stressful environments. Unlike sterols, the effects of hopanoids on membranes can vary because of their diversity. While it is understood that hopanoids can indirectly tune membrane physical properties, little is known on the role that hopanoids may play in affecting the organization and behavior of bacterial membrane proteins. In this work we used enhanced sampling molecular dynamics (MD) simulations to characterize the thermodynamics of binding of two unique hopanoids, diploptene (DPT) and bacteriohopanetetrol (BHT), to the bacterial proton pump, proteorhodopsin (PR), in a model membrane composed of 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphoethanolamine (POPE) and 1‐palmitoyl‐2‐oleoyl‐sn‐3‐phosphoglycerol (POPG). PR was chosen because its membrane environment can tune the equilibrium between monomeric and oligomeric states. Furthermore, its proton pumping efficiency is orders of magnitude slower in the oligomeric form. Our results reveal that the biophysical interactions of BHT and DPT with PR are distinct, leading to fundamentally different free energies of binding. These differences also drive sampling of different dimeric complexes of PR. BHT has the ability to intercalate between monomers in the dimeric interface, whereas DPT shifts dimerization interactions via packing of the interleaflet region of the membrane. Our results show a direct relationship between hopanoid structure and lateral organization of PR, providing a first glimpse at how these bacterial analogues to eukaryotic sterols produce very similar biophysical effects within the cell membrane.