bims-tricox 2024-04-28 papers

Issue of 2024‒04‒28
three papers selected by
Yash Verma, University of Zurich

FEBS Lett. 2024 Apr 25.

Insights into conformational changes in cytochrome b during the early steps of its maturation.

Membrane proteins carrying redox cofactors are key subunits of respiratory chain complexes, yet the exact path of their folding and maturation remains poorly understood. Here, using cryo-EM and structure prediction via Alphafold2, we generated models of early assembly intermediates of cytochrome b (Cytb), a central subunit of complex III. The predicted structure of the first assembly intermediate suggests how the binding of Cytb to the assembly factor Cbp3-Cbp6 imposes an open configuration to facilitate the acquisition of its heme cofactors. Moreover, structure predictions of the second intermediate indicate how hemes get stabilized by binding of the assembly factor Cbp4, with a concomitant weakening of the contact between Cbp3-Cbp6 and Cytb, preparing for the release of the fully hemylated protein from the assembly factors.

Keywords: biogenesis; cytochrome b; membrane protein assembly; mitochondria; respiratory chain

DOI: https://doi.org/10.1002/1873-3468.14888

FEBS Open Bio. 2024 Apr 25.

Protein insertion into the inner membrane of mitochondria: routes and mechanisms.

Büsra Kizmaz, Annika Nutz, Annika Egeler, Johannes M Herrmann.

The inner membrane of mitochondria contains hundreds of different integral membrane proteins. These proteins transport molecules into and out of the matrix, they carry out multifold catalytic reactions and they promote the biogenesis or degradation of mitochondrial constituents. Most inner membrane proteins are encoded by nuclear genes and synthesized in the cytosol from where they are imported into mitochondria by translocases in the outer and inner membrane. Three different import routes direct proteins into the inner membrane and allow them to acquire their appropriate membrane topology. First, mitochondrial import intermediates can be arrested at the level of the TIM23 inner membrane translocase by a stop-transfer sequence to reach the inner membrane by lateral insertion. Second, proteins can be fully translocated through the TIM23 complex into the matrix from where they insert into the inner membrane in an export-like reaction. Carriers and other polytopic membrane proteins embark on a third insertion pathway: these hydrophobic proteins employ the specialized TIM22 translocase to insert from the intermembrane space (IMS) into the inner membrane. This review article describes these three targeting routes and provides an overview of the machinery that promotes the topogenesis of mitochondrial inner membrane proteins.

Keywords: TIM22 complex; TIM23 complex; carrier proteins; membrane proteins; mitochondria; protein import

DOI: https://doi.org/10.1002/2211-5463.13806

Cell Rep Methods. 2024 Apr 22. pii: S2667-2375(24)00092-4. [Epub ahead of print]4(4): 100761

Methodological advances enabled by the construction of a synthetic yeast genome.

Daniel Schindler, Roy S K Walker, Yizhi Cai.

The international Synthetic Yeast Project (Sc2.0) aims to construct the first synthetic designer eukaryote genome. Over the past few years, the Sc2.0 consortium has achieved several significant milestones by synthesizing and characterizing all 16 nuclear chromosomes of the yeast Saccharomyces cerevisiae, as well as a 17thde novo neochromosome containing all nuclear tRNA genes. In this commentary, we discuss the recent technological advances achieved in this project and provide a perspective on how they will impact the emerging field of synthetic genomics in the future.

DOI: https://doi.org/10.1016/j.crmeth.2024.100761