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-Structure paper
タイトル | Structural insights into the mechanism and dynamics of proteorhodopsin biogenesis and retinal scavenging. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 6950, Year 2024 |
掲載日 | 2024年8月13日 |
著者 | Stephan Hirschi / Thomas Lemmin / Nooraldeen Ayoub / David Kalbermatter / Daniele Pellegata / Zöhre Ucurum / Jürg Gertsch / Dimitrios Fotiadis / |
PubMed 要旨 | Microbial ion-pumping rhodopsins (MRs) are extensively studied retinal-binding membrane proteins. However, their biogenesis, including oligomerisation and retinal incorporation, remains poorly ...Microbial ion-pumping rhodopsins (MRs) are extensively studied retinal-binding membrane proteins. However, their biogenesis, including oligomerisation and retinal incorporation, remains poorly understood. The bacterial green-light absorbing proton pump proteorhodopsin (GPR) has emerged as a model protein for MRs and is used here to address these open questions using cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulations. Specifically, conflicting studies regarding GPR stoichiometry reported pentamer and hexamer mixtures without providing possible assembly mechanisms. We report the pentameric and hexameric cryo-EM structures of a GPR mutant, uncovering the role of the unprocessed N-terminal signal peptide in the assembly of hexameric GPR. Furthermore, certain proteorhodopsin-expressing bacteria lack retinal biosynthesis pathways, suggesting that they scavenge the cofactor from their environment. We shed light on this hypothesis by solving the cryo-EM structure of retinal-free proteoopsin, which together with mass spectrometry and MD simulations suggests that decanoate serves as a temporary placeholder for retinal in the chromophore binding pocket. Further MD simulations elucidate possible pathways for the exchange of decanoate and retinal, offering a mechanism for retinal scavenging. Collectively, our findings provide insights into the biogenesis of MRs, including their oligomeric assembly, variations in protomer stoichiometry and retinal incorporation through a potential cofactor scavenging mechanism. |
リンク | Nat Commun / PubMed:39138159 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.82 - 3.54 Å |
構造データ | EMDB-16759, PDB-8cnk: EMDB-16795, PDB-8cqc: EMDB-16796, PDB-8cqd: |
化合物 | ChemComp-DKA: ChemComp-RET: ChemComp-HOH: |
由来 |
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キーワード | PROTON TRANSPORT / Membrane protein / Light-driven proton pump / Proteorhodopsin / Proteoopsin |