Rathod, A. K. | bioRxiv Science

bioRxiv2024

Kingdom-specific lipid unsaturation shapes up sequence evolution in membrane arm subunits of eukaryotic respiratory complexes

Sequence evolution of protein complexes (PCs) is constrained by protein-protein interactions (PPIs). PPI-interfaces are predominantly conserved and hotspots for disease-related mutations. How lipid-protein interactions (LPIs) constrain sequence evolution of membrane- PCs? We explore Respiratory Complexes (RCs) as a case study as these allow to compare sequence evolution in subunits exposed to both lipid-rich inner-mitochondrial membrane (IMM) and aqueous matrix. We find that lipid-exposed surfaces of the IMM-subunits but not of the matrix subunits are populated with non-PPI disease-causing mutations signifying LPIs in stabilizing RCs. Further, IMM-subunits including their exposed surfaces show high intra- kingdom sequence conservation but remarkably diverge beyond. Molecular Dynamics simulation suggests contrasting LPIs of structurally superimposable but sequence-wise diverged IMM-exposed helices of Complex I (CI) subunit Ndufa1 from human and Arabidopsis depending on kingdom-specific unsaturation of cardiolipin fatty acyl chains. in cellulo assays consolidate inter-kingdom incompatibility of Ndufa1-helices due to the lipid- exposed amino acids. Plant-specific unsaturated fatty acids in human cells also trigger CI- instability. Taken together, we posit that altered LPIs calibrate sequence evolution at the IMM-arms of eukaryotic RCs.

cell biology↗

bioRxiv2022

Phase transition in atomistic simulations of model membrane with thylakoid lipids of red algae

Marine algae are diverse photosynthetic organisms, profoundly rich in bioactive compounds. Temperature is a major factor in algal cultivation and biomass production. At the cellular level, the change of temperature is reflected in oscillating algal lipid/fatty acid profile and inhibition of photosynthetic activities. The function of thylakoid membrane system is intimately dependent on its lipid matrix, however the molecular organization of these lipid membranes and particularly their adaptive arrangements under temperature stress remain largely unexplored. The present work employing extensive atomistic simulations provides the first atomistic view of the phase transition and domain coexistence in model membrane composed of thylakoid lipids of a marine alga, between 10-40 {degrees}C. The model membrane undergoes a transition from a gel-like phase at 10-15 {degrees}C to a homogeneous liquid-disordered phase at 40 {degrees}C. Clear evidences of spontaneous phase separation into coexisting nanoscale domains are detected at intermediate temperatures. Particularly at 25-30 {degrees}C, we identified the formation of a stable rippled phase, where the gel-like domains rich in saturated and nearly hexagonally packed lipids separated from fluid-like domains enriched in lipids containing polyunsaturated chains. Cholesterol impairs the phase transition and the emergence of domains, and induces a fairly uniform liquid-ordered phase in the membrane over the temperatures studied. The results have implications in understanding the role of lipids in temperature adaptation in algal.

biophysics↗