Protein translocation across the cellular membranes is an ubiquitous and crucial activity of cells. This process is mediated by translocases that consist of a protein conducting channel and an associated motor protein. Motor proteins interact with protein substrates and utilize the free energy of ATP binding and hydrolysis for protein unfolding, translocation and unbinding. Since motor proteins are found either at the cis- or trans-side of the membrane, different mechanisms for translocation have been proposed. In the Power stroke model, cis-acting motors are thought to push, while trans-motors pull on the substrate protein during translocation. In the Brownian ratchet model, translocation occurs by diffusion of the unfolded polypeptide through the translocation pore while directionality is achieved by trapping and refolding. Recent insights in the structure and function of the molecular motors suggest that different mechanisms can be employed simultaneously.
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http://dx.doi.org/10.1016/j.febslet.2007.04.015 | DOI Listing |
J Med Chem
January 2025
Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Xi'an 710021, China.
Multidrug-resistant (MDR) bacteria pose a global health threat, underscoring the need for new antibiotics. Lefamulin, the first novel-mechanism antibiotic approved by the FDA in decades, showcases pleuromutilins' promise due to low mutation frequency. However, their clinical use is limited by poor pharmacokinetics and organ toxicity.
View Article and Find Full Text PDFSci Adv
January 2025
Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
The rare metal element molybdenum functions as a cofactor in molybdoenzymes that are essential to life in almost all living things. Molybdate can be captured by the periplasmic substrate-binding protein ModA of ModABC transport system in bacteria. We demonstrate that ModA plays crucial roles in growth, multiple metabolic pathways, and ROS tolerance in .
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91052 Erlangen, Germany.
Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, the molecular mechanisms of barrier failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in intestinal epithelial cells (IECs) of patients with IBD and show that impaired fusion is sufficient to drive chronic intestinal inflammation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430070, People's Republic of China.
Interferon regulatory factor 3 (IRF3) is the key transcription factor in the type I IFN signaling pathway, whose activation is regulated by multiple posttranslational modifications. Here, we identify SMYD3, a lysine methyltransferase, as a negative regulator of IRF3. SMYD3 interacts with IRF3 and catalyzes the dimethylation of IRF3 at lysine 39.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210.
The Munc13/UNC-13 family protein Ync13 is essential for septum integrity and cytokinesis in fission yeast. To further explore the mechanism of Ync13 functions, spontaneous suppressors of mutants, which can suppress the colony-formation defects and lysis phenotype of mutant cells, are isolated and characterized. One of the suppressor mutants, -, shows defects in the cytokinetic contractile ring constriction, septation, and daughter-cell separation, similar to mutant.
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