@article{14040, abstract = {Robust oxygenic photosynthesis requires a suite of accessory factors to ensure efficient assembly and repair of the oxygen-evolving photosystem two (PSII) complex. The highly conserved Ycf48 assembly factor binds to the newly synthesized D1 reaction center polypeptide and promotes the initial steps of PSII assembly, but its binding site is unclear. Here we use cryo-electron microscopy to determine the structure of a cyanobacterial PSII D1/D2 reaction center assembly complex with Ycf48 attached. Ycf48, a 7-bladed beta propeller, binds to the amino-acid residues of D1 that ultimately ligate the water-oxidising Mn4CaO5 cluster, thereby preventing the premature binding of Mn2+ and Ca2+ ions and protecting the site from damage. Interactions with D2 help explain how Ycf48 promotes assembly of the D1/D2 complex. Overall, our work provides valuable insights into the early stages of PSII assembly and the structural changes that create the binding site for the Mn4CaO5 cluster.}, author = {Zhao, Ziyu and Vercellino, Irene and Knoppová, Jana and Sobotka, Roman and Murray, James W. and Nixon, Peter J. and Sazanov, Leonid A and Komenda, Josef}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis}}, doi = {10.1038/s41467-023-40388-6}, volume = {14}, year = {2023}, } @article{10182, abstract = {The mitochondrial oxidative phosphorylation system is central to cellular metabolism. It comprises five enzymatic complexes and two mobile electron carriers that work in a mitochondrial respiratory chain. By coupling the oxidation of reducing equivalents coming into mitochondria to the generation and subsequent dissipation of a proton gradient across the inner mitochondrial membrane, this electron transport chain drives the production of ATP, which is then used as a primary energy carrier in virtually all cellular processes. Minimal perturbations of the respiratory chain activity are linked to diseases; therefore, it is necessary to understand how these complexes are assembled and regulated and how they function. In this Review, we outline the latest assembly models for each individual complex, and we also highlight the recent discoveries indicating that the formation of larger assemblies, known as respiratory supercomplexes, originates from the association of the intermediates of individual complexes. We then discuss how recent cryo-electron microscopy structures have been key to answering open questions on the function of the electron transport chain in mitochondrial respiration and how supercomplexes and other factors, including metabolites, can regulate the activity of the single complexes. When relevant, we discuss how these mechanisms contribute to physiology and outline their deregulation in human diseases.}, author = {Vercellino, Irene and Sazanov, Leonid A}, issn = {1471-0080}, journal = {Nature Reviews Molecular Cell Biology}, pages = {141–161}, publisher = {Springer Nature}, title = {{The assembly, regulation and function of the mitochondrial respiratory chain}}, doi = {10.1038/s41580-021-00415-0}, volume = {23}, year = {2022}, } @article{12282, abstract = {From a simple thought to a multicellular movement}, author = {Amberg, Nicole and Stouffer, Melissa A and Vercellino, Irene}, issn = {1477-9137}, journal = {Journal of Cell Science}, number = {8}, publisher = {The Company of Biologists}, title = {{Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole}}, doi = {10.1242/jcs.260017}, volume = {135}, year = {2022}, } @article{10146, abstract = {The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and plants13, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain.}, author = {Vercellino, Irene and Sazanov, Leonid A}, issn = {1476-4687}, journal = {Nature}, number = {7880}, pages = {364--367}, publisher = {Springer Nature}, title = {{Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV}}, doi = {10.1038/s41586-021-03927-z}, volume = {598}, year = {2021}, } @article{6919, author = {Qi, Chao and Minin, Giulio Di and Vercellino, Irene and Wutz, Anton and Korkhov, Volodymyr M.}, issn = {23752548}, journal = {Science Advances}, number = {9}, publisher = {American Association for the Advancement of Science}, title = {{Structural basis of sterol recognition by human hedgehog receptor PTCH1}}, doi = {10.1126/sciadv.aaw6490}, volume = {5}, year = {2019}, }