Maslennikova et al. identify the ER membrane protein CLCC1 as an interaction partner of the dystonia-linked AAA+ ATPase Torsin1A. Torsin1A sustains the function of CLCC1, which is proposed to facilitate fusion of the nuclear envelope during NPC biogenesis by forming an oligomer that promotes lipid bilayer approach and remodeling.

The Sec translocon and the YidC/Oxa1-type insertases universally mediate biogenesis of α-helical membrane proteins, but the molecular basis of their cooperation has remained disputed. Recent discovery...

SUMMARYClass I fusion proteins are trimeric viral membrane proteins that mediate fusion between the virion and cellular membranes. In their prefusion state, they comprise three domains: a globular “he...

Yan et al. reveal the structure of the ER-resident Erlin1/2 complex, showing how it assembles into a cage-like architecture that organizes functional membrane microdomains on the ER membrane and regulates cargo protein accessibility. These findings provide a structural framework for understanding Erlin-mediated processes on the ER membrane.

Viral protein biogenesis underpins every viral life cycle stage, and elucidating these processes could reveal fundamental principles of virus host interaction, and vulnerabilities amenable to therapeutic targeting. Here we apply biophysical, molecular, and cell biology techniques to investigate the insertion, folding, and oligomerization of the SARS CoV 2 M protein. We describe the sequential cotranslational insertion of the hydrophobic core, and demonstrate that the cytosolic C terminal domain undergoes slower adoption of its tertiary structure. Additionally, we characterize how the transmembrane domain bundle facilitates M protein oligomerization. Our results reveal a hydrophobic residue cluster that is essential for protein folding and co-translational dimerization. Additionally, we identify the cellular machinery responsible for targeting and inserting the M protein into the ER membrane, and chaperones and cofactors that may contribute to proper folding. ### Competing Interest Statement The authors have declared no competing interest. Spanish Ministry of Science, Innovation and Universities Generalitat Valenciana European Union NextGenerationEU/PRTR University of Valencia Spanish Ministry of Science and Innovation Wellcome Trust Cancer Research UK UK Medical Research Council Knut and Alice Wallenberg Foundation Novo Nordisk Fund Swedish Research Council National Institutes of Health

Viral protein biogenesis underpins every viral life cycle stage, and elucidating these processes could reveal fundamental principles of virus host interaction, and vulnerabilities amenable to therapeutic targeting. Here we apply biophysical, molecular, and cell biology techniques to investigate the insertion, folding, and oligomerization of the SARS CoV 2 M protein. We describe the sequential cotranslational insertion of the hydrophobic core, and demonstrate that the cytosolic C terminal domain undergoes slower adoption of its tertiary structure. Additionally, we characterize how the transmembrane domain bundle facilitates M protein oligomerization. Our results reveal a hydrophobic residue cluster that is essential for protein folding and co-translational dimerization. Additionally, we identify the cellular machinery responsible for targeting and inserting the M protein into the ER membrane, and chaperones and cofactors that may contribute to proper folding. ### Competing Interest Statement The authors have declared no competing interest. Spanish Ministry of Science, Innovation and Universities Generalitat Valenciana European Union NextGenerationEU/PRTR University of Valencia Spanish Ministry of Science and Innovation Wellcome Trust Cancer Research UK UK Medical Research Council Knut and Alice Wallenberg Foundation Novo Nordisk Fund Swedish Research Council National Institutes of Health

Coupling an optogenetic lipid-modifying enzyme with proximity labeling reveals protein networks and mechanisms regulating lipid homeostasis in the membranes of target organelles.

Mitochondria, which evolved from symbiotic bacteria, possess their own genomes (mtDNA) and support independent transcription and translation within the organelle. Given the essential role of mtDNA in ...

<p>Research conducted by the University of Valencia and the Spanish National Research Council (CSIC) has revealed that a previously little-studied region of the SARS-CoV-2 spike protein is crucial for...

Una investigació de la Universitat de València i del Consell Superior d’Investigacions Científiques (CSIC) ha descobert que una regió fins ara poc estudiada de la proteïna espícula (spike) del coronavirus SARS-CoV-2 resulta vital perquè el...

Synthetic carbohydrate receptors prevent viral infections by binding to conserved enveloped virus glycans on viral surfaces.

The GroEL/ES chaperonin can act during protein synthesis to promote folding. Here, Roeselová et al. show how GroEL captures, remodels and sequesters nascent proteins in its central chamber, while they...

Nature - The structural mechanism of a natively isolated GRP94 folding intermediate tethered to a CCDC134-bound translocon is described, revealing how the nascent chain remodels the translocon to...

Structural insights into SARS and MERS coronavirus membrane protein reveals differences and conserved sites of an inhibitor binding pocket, aiding in the design of broad-spectrum and specific antivira...

A study using SARS-CoV-2 pseudotyped viruses and testing Spike protein fusion capacity demonstrates that its transmembrane domain is essential for viral entry and suggests the presence of an intramemb...

Misfolded or unassembled membrane proteins in the endoplasmic reticulum (ER) are polyubiquitinated, translocated into the cytosol, and degraded by the proteasome, a poorly understood process that is c...

The authors use selective ribosome profiling to define how and when factors for N-glycosylation and membrane insertion engage and disengage from the core Sec61 translocation channel during biogenesis ...

Bacteria in the gut use an unusual molecular apparatus to insert complex proteins into their outer membrane.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding in...

Leder et al. show that the chaperones PDIA6, Hsp70 BiP, ERdj3, PDIA1 and Hsp90 form co-condensates within the endoplasmic reticulum, enhancing folding and preventing misfolding of client proteins.

FoF1-ATP synthase converts proton motive force into ATP, with the H+/ATP ratio typically ranging from 2.7 to 5. Here, the authors engineered this enzyme to form multiple peripheral stalks, achieving a...

Defining the minimal genetic requirements for cellular life remains a fundamental question in biology. Genomic exploration continually reveals novel microbial lineages, often exhibiting extreme genome...

Cryo-electron tomography has emerged as powerful technology for in-cell structural biology, and in combination with breakthroughs in protein structure prediction, offers a unique opportunity for illum...

The universally conserved Sec translocon and the YidC/Oxa1-type insertases mediate biogenesis of alpha-helical membrane proteins, but the molecular basis of their cooperation has remained disputed over decades. A recent discovery of a multi-subunit insertase in eukaryotes has raised the question about the architecture of the putative bacterial ortholog SecYEG-YidC and its functional mechanism. Here, we combine cryogenic electron microscopy with cell-free protein synthesis in nanodiscs to visualize biogenesis of the polytopic membrane protein NuoK, the subunit K of NADH-quinone oxidoreductase, that requires both SecYEG and YidC for insertion. We demonstrate that YidC is recruited to the back of the translocon at the late stage of the substrate insertion, in resemblance to the eukaryotic system, and in vivo experiments indicate that the complex assembly is vital for the cells. The nascent chain does not utilize the lateral gate of SecYEG, but enters the lipid membrane at the SecYE-YidC interface, with YidC being the primary insertase. SecYEG-YidC complex promotes folding of the nascent helices at the interface prior their insertion, so the examined cellular pathway follows the fundamental thermodynamic principles of membrane protein folding. Our data provide the first detailed insight on the elusive insertase machinery in the physiologically relevant environment, highlight the importance of the nascent chain for its assembly, and prove the evolutionary conservation of the gate-independent insertion route. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, Ke1879/3, 267205415 (CRC 1208) European Research Council, https://ror.org/0472cxd90, CRYOTRANSLATION

Nature - High-throughput screening and hit optimization have led to the development of a small molecule, CIM-834, that targets the SARS-CoV-2 membrane protein and blocks assembly of the virus.

A biological hydrophobicity scale reveals amino acid partition preferences in water, membrane surfaces, and transmembrane regions.