Archaeal Lipids Regulating the Trimeric Structure Dynamics of Bacteriorhodopsin for Efficient Proton Release and Uptake

Abstract

S-TGA-1 and PGP-Me are native archaeal lipids associated with the bacteriorhodopsin (bR) trimer and contribute to protein stabilization and native dynamics for proton transfer. However, little is known about the underlying molecular mechanism of how these lipids regulate bR trimerization and efficient photocycling. Here, we explored the specific binding of S-TGA-1 and PGP-Me with the bR trimer and elucidated how specific interactions modulate the bR trimeric structure and proton release and uptake using long-term atomistic molecular dynamic simulations. Our results showed that S-TGA-1 and PGP-Me are essential for stabilizing the bR trimer and maintaining the coherent conformational dynamics necessary for proton transfer. The specific binding of S-TGA-1 with W80 and K129 regulates proton release on the extracellular surface by forming a “Glu-shared” model. The interaction of PGP-Me with K40 ensures proton uptake by accommodating the conformation of the helices to recruit enough water molecules on the cytoplasmic side. The present study results could fill in the theoretical gaps of studies on the functional role of archaeal lipids and could provide a reference for other membrane proteins containing similar archaeal lipids.

Uniaxial Symmetry Breaking in Bacteriorhodopsin at the Thermal Phase Transition of Lipids of Purple Membranes

“…What is more important is that the hexagonal crystal lattice was well preserved only when either of the two phospholipids was present in bR reconstituted in lipid vesicles . Both the major phospholipid (PGP-Me) and the major triglycosylated lipid (S-TGA-1) proved crucial to maintain the aggregated state of bR in the crystal lattice, as the former can adjoin two adjacent monomers, while the latter, by virtue of its outstanding diffraction pattern, can connect the bR trimers, as it resides in the trimeric spaces, and proved thus crucial in this trimerization. , With no doubts, the lipid–protein contact , plays an important role in maintaining the crystal lattice of bR. Correlation of thermally induced structural changes (i.e., phase transition relevance) to aggregation changes in bR (i.e., axial symmetry relevance) might necessitate the indispensability role of mediating lipids to keep such correlation maintained.…”