Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | Artículo científico |
| Lenguaje: | en |
| Publicado: |
Nature communications
2025
|
| Materias: | |
| Acceso en línea: | https://pubmed.ncbi.nlm.nih.gov/40016208/ |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| _version_ | 1868266237321019392 |
|---|---|
| author | Gupta, Pooja Chakroborty, Sristi Rathod, Arun K Kumar, K Ranjith Bhat, Shreya Ghosh, Suparna Rao T, Pallavi Yele, Kameshwari Bakthisaran, Raman Nagaraj, R Manna, Moutusi Raychaudhuri, Swasti |
| author_facet | Gupta, Pooja Chakroborty, Sristi Rathod, Arun K Kumar, K Ranjith Bhat, Shreya Ghosh, Suparna Rao T, Pallavi Yele, Kameshwari Bakthisaran, Raman Nagaraj, R Manna, Moutusi Raychaudhuri, Swasti Gupta, Pooja Chakroborty, Sristi Rathod, Arun K Kumar, K Ranjith Bhat, Shreya Ghosh, Suparna Rao T, Pallavi Yele, Kameshwari Bakthisaran, Raman Nagaraj, R Manna, Moutusi Raychaudhuri, Swasti |
| collection | PubMed - marine biology |
| contents | Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes. Gupta, Pooja Chakroborty, Sristi Rathod, Arun K Kumar, K Ranjith Bhat, Shreya Ghosh, Suparna Rao T, Pallavi Yele, Kameshwari Bakthisaran, Raman Nagaraj, R Manna, Moutusi Raychaudhuri, Swasti Humans Evolution, Molecular Molecular Dynamics Simulation Arabidopsis Mitochondrial Membranes Electron Transport Complex I Cardiolipins Protein Subunits Mutation Lipids Amino Acid Sequence 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 do 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 lipids in inner-mitochondrial membrane (IMM) and lipid-free 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. |
| format | Artículo científico |
| id | pubmed_40016208 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Nature communications |
| record_format | pubmed |
| spellingShingle | Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes. Gupta, Pooja Chakroborty, Sristi Rathod, Arun K Kumar, K Ranjith Bhat, Shreya Ghosh, Suparna Rao T, Pallavi Yele, Kameshwari Bakthisaran, Raman Nagaraj, R Manna, Moutusi Raychaudhuri, Swasti Humans Evolution, Molecular Molecular Dynamics Simulation Arabidopsis Mitochondrial Membranes Electron Transport Complex I Cardiolipins Protein Subunits Mutation Lipids Amino Acid Sequence Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes. Gupta, Pooja Chakroborty, Sristi Rathod, Arun K Kumar, K Ranjith Bhat, Shreya Ghosh, Suparna Rao T, Pallavi Yele, Kameshwari Bakthisaran, Raman Nagaraj, R Manna, Moutusi Raychaudhuri, Swasti Humans Evolution, Molecular Molecular Dynamics Simulation Arabidopsis Mitochondrial Membranes Electron Transport Complex I Cardiolipins Protein Subunits Mutation Lipids Amino Acid Sequence 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 do 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 lipids in inner-mitochondrial membrane (IMM) and lipid-free 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. |
| title | Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes. |
| topic | Humans Evolution, Molecular Molecular Dynamics Simulation Arabidopsis Mitochondrial Membranes Electron Transport Complex I Cardiolipins Protein Subunits Mutation Lipids Amino Acid Sequence |
| url | https://pubmed.ncbi.nlm.nih.gov/40016208/ |