Article
Biology
William J. Allen, Robin A. Corey, Daniel W. Watkins, A. Sofia F. Oliveira, Kiel Hards, Gregory M. Cook, Ian Collinson
Summary: Transport of proteins across and into membranes is a fundamental process in biology. Recent studies have shown that the diffusion of arginine residues limits pre-protein transport, while lysine can be transported across membranes in its neutral form. These findings have implications for understanding the mechanism of protein secretion and suggest a potential role of proton-motive force in aiding transport.
Article
Multidisciplinary Sciences
Linlin Dong, Song Yang, Jingxia Chen, Xiaofei Wu, Dongjie Sun, Chen Song, Long Li
Summary: Secretory proteins are translocated across lipid membranes via protein-conducting channels called SecY in prokaryotes and Sec61 in eukaryotes. SecA, an ATPase, drives the posttranslational translocation of secretory proteins in bacteria through the SecY channel. The mechanism of how SecA moves a polypeptide chain through the SecY channel is poorly understood. This study presents electron cryomicroscopy structures of the active SecA-SecY translocon with a polypeptide substrate, revealing the conformational changes of SecA and the structural basis of polypeptide movement during translocation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Physiology
Sharbani Kaushik, Haoze He, Ross E. Dalbey
Summary: This review summarizes the crucial role of signal peptides in protein export and membrane protein insertion, as well as their function as key factors for protein targeting and translocation machinery activation. The importance of signal peptide removal and degradation, as well as the emerging research on signal peptidases as novel targets for antibiotic development, are also discussed.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Immunology
Samer Halabi, Jim Kaufman
Summary: The functions and structures of MHC and MHC molecules have been extensively studied, and many findings are considered as established knowledge. However, there is significant variation of MHC and MHC molecules in non-mammalian vertebrates, particularly in domestic chickens. Studies on chicken class I and class II molecules have revealed unexpected structural features, which could contribute to a deeper understanding of how MHC molecules bind and present peptides to lymphocytes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Pamela O'Neill, Rajesh K. Mistry, Adam J. Brown, David C. James
Summary: This study develops a toolkit of signal peptide elements to enhance the production of biopharmaceutical proteins in Chinese hamster ovary cell factories. Machine learning is used to predict the performance of discrete signal peptide elements in driving translocation of specific protein products. In vitro testing combined with in silico design enables the rapid identification of product-specific signal peptide solutions.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Zidong Jiang, Lujia Zhang, Wei Zhou, Hui Li, Yuanyi Li, Weichuang Qin, Fengqing Wang, Dongzhi Wei, Bei Gao
Summary: In this study, a binding structure between SecA and a signal peptide was established, and a grinding approach was used to modify them, leading to improved protein secretion efficiency. A bidirectional grinding strategy was also developed to enhance the secretion system, resulting in a significantly increased protein activity. This research provides a novel and promising strategy for optimizing protein secretion and production in B. subtilis.
BIOCHEMICAL ENGINEERING JOURNAL
(2023)
Article
Cell Biology
Srinath Krishnamurthy, Marios-Frantzeskos Sardis, Nikolaos Eleftheriadis, Katerina E. Chatzi, Jochem H. Smit, Konstantina Karathanou, Giorgos Gouridis, Athina G. Portaliou, Ana-Nicoleta Bondar, Spyridoula Karamanou, Anastassios Economou
Summary: Protein machines undergo conformational motions to interact with and manipulate polymeric substrates. The intrinsic dynamics of Sec translocase ATPase, SecA, and the binding of preproteins combine to achieve translocation. This universal mechanism allows any preprotein to undergo translocation and be secreted.
Article
Multidisciplinary Sciences
Samar Alanazi, Wasim Feroz, Rosalin J. Mishra, Mary Kate T. Kilroy, Hima Patel, Long Yuan, Sarah Storr, Joan Garrett
Summary: HER2 is over-expressed in 15% to 20% of breast cancers and HER3 plays a critical role in HER2 mediated tumorigenesis. In this study, proteins that bound to HER3 when the HER family was inhibited by the pan-HER inhibitor neratinib were identified. Non-muscle myosin IIA (NMIIA) was found to increase upon neratinib treatment and its loss reduces HER2+ breast cancer growth. This study highlights the importance of HER3 and NMIIA in HER2+ breast cancer progression.
Review
Biochemistry & Molecular Biology
A. Manuel Liaci, Friedrich Forster
Summary: Cleavable and non-cleavable signal sequences target a quarter of the human proteome to the ER. Interaction between these signal sequences and ER targeting machinery determines protein location and translocation fidelity, as discussed in recent insights from structural biology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Inbal Wortzel, Galia Maik-Rachline, Suresh Singh Yadav, Tamar Hanoch, Rony Seger
Summary: This study reveals a novel mechanism of Golgi apparatus destabilization early in mitosis through the regulation of HOOK3 phosphorylation by ERK1c, facilitating mitotic progression.
Review
Biochemistry & Molecular Biology
Pratiti Bhadra, Volkhard Helms
Summary: Recent molecular modeling and simulation studies have focused on the dynamics and mechanisms of the Sec translocon, exploring the process of protein translocation into the endoplasmic reticulum and bacterial periplasm. Computational studies have investigated the conformational dynamics of the translocon in various states and addressed mechanistic issues such as membrane insertion and peptide recognition. Additionally, simulations have examined how accessory proteins impact Sec61 conformation during translation pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Jessica Fiebelkow, Andre Guendel, Beate Guendel, Nora Mehwald, Tomasz Jetka, Michal Komorowski, Steffen Waldherr, Fred Schaper, Anna Dittrich
Summary: The study shows that SHP2 not only increases robustness of basal and cytokine-induced STAT3 activity, but also ensures information transmission. SHP2 increases the dynamic range of pathway activation in JAK/STAT signalling, contributing to communication in multicellular organisms.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Biology
Riti Gupta, Dmitri Toptygin, Christian M. Kaiser
Summary: This study presents a method for real-time measurement of protein translocation, allowing high-resolution kinetics of the actual translocation process to be resolved. By developing a detailed kinetic model, detailed mechanistic analyses of Sec-dependent protein translocation can be conducted.
Article
Oncology
Anjan K. Pradhan, Praveen Bhoopathi, Santanu Maji, Amit Kumar, Chunqing Guo, Padmanabhan Mannangatti, Jiong Li, Xiang-Yang Wang, Devanand Sarkar, Luni Emdad, Swadesh K. Das, Paul B. Fisher
Summary: Researchers engineered a designer cytokine called M7S (IL-24S) to enhance the therapeutic efficacy of MDA-7 (IL-24) in cancer treatment. M7S showed superior anti-tumor effects compared to MDA-7 and when combined with an immune checkpoint inhibitor, it reduced tumor progression significantly.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Sang-Hyeon Mun, Chang-Seok Lee, Hyun Jin Kim, Jiye Kim, Haena Lee, Jihye Yang, Sin-Hyeo Im, Joung-Hun Kim, Je Kyung Seong, Cheol-Sang Hwang
Summary: The cytosol-retained POMC induces ER stress and ferroptotic cell death. It accelerates degradation of the glutathione peroxidase Gpx4, a core regulator of ferroptosis, via chaperone-mediated autophagy. The Marchf6 E3 ubiquitin ligase mediates the degradation of cytosol-retained POMC, preventing ER stress and ferroptosis. POMC-Cre-mediated Marchf6-deficient mice exhibit hyperphagia, reduced energy expenditure, and weight gain.