Review
Biochemistry & Molecular Biology
Sung-jun Jung, Hyun Kim
Summary: Sec62 and Sec63 interact with the Sec61 channel to form the Sec complex, mediating the translocation of a subset of proteins across the ER membrane. Previous understanding suggested two distinct pathways for ER protein targeting and translocation, but recent studies have shown that the process through the Sec translocon is more intricate than previously thought.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Eva Pauwels, Ralf Schuelein, Kurt Vermeire
Summary: The process of protein translocation across the ER is mediated by the Sec61 translocon complex, which is challenging to purify and reconstitute, making it difficult to screen for small molecule inhibitors. However, these inhibitors have potential as valuable tools in cell biology and as novel anticancer drugs. Recent screening strategies may also help in identifying new antibiotic drugs targeting the bacterial Sec61 complex counterpart, SecYEG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Andrea Tirincsi, Mark Sicking, Drazena Hadzibeganovic, Sarah Hassdenteufel, Sven Lang
Summary: Cells use a variety of components to ensure the safe transport of proteins in the endoplasmic reticulum. Different targeting routes and protein translocases have preferences for specific targeting signals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Baiying Li, Yonglun Zeng, Sze Wan Lo, Yusong Guo, Liwen Jiang
Summary: This article describes an Arabidopsis-derived in vitro vesicle formation system for the reconstitution, purification, and characterization of plant-derived COPII vesicles. The method involves the isolation of microsomes and cytosol from suspension-cultured cells, in vitro COPII vesicle reconstitution and purification, and biochemical and microscopic analysis using specific antibodies. The entire procedure takes approximately 18-20 hours of operation time and allows plant researchers without specific expertise to achieve organelle purification or vesicle reconstitution for further characterization.
Article
Multidisciplinary Sciences
Hyunwoo Kim, Seowhang Lee, Youngsoo Jun, Changwook Lee
Summary: This study reveals the molecular mechanism and structural basis of how MIGA2 regulates ERMCS formation and facilitates lipid trafficking at ERMCS.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Eva Pauwels, Neesha R. Shewakramani, Brent De Wijngaert, Anita Camps, Becky Provinciael, Joren Stroobants, Kai -Uwe Kalies, Enno Hartmann, Piet Maes, Kurt Vermeire, Kalyan Das
Summary: During cotranslational translocation, the signal peptide of a nascent chain binds Sec61 translocon to initiate protein transport through the endoplasmic reticulum (ER) membrane. Our cryo-electron microscopy structure of ribosome-Sec61 shows binding of an ordered heterotetrameric translocon-associated protein (TRAP) complex, in which TRAP-gamma is anchored at two adjacent positions of 28S ribosomal RNA and interacts with ribosomal protein L38 and Sec61 alpha/gamma. Four transmembrane helices (TMHs) of TRAP-gamma cluster with one C-terminal helix of each alpha, 13, and delta subunits.
Review
Biochemistry & Molecular Biology
Martin R. Pool
Summary: The endoplasmic reticulum serves as the entry point for the secretory pathway, responsible for targeting proteins to their appropriate destinations. This targeting process involves the recognition of specific targeting signals and their subsequent delivery to the translocases present at the ER membrane. Targeting is typically mediated by cleavable N-terminal hydrophobic signal sequences or internal membrane anchor sequences, and the location and features of the targeting sequence determine which targeting pathway substrates are used.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Luka Smalinskait, Min Kyung Kim, Aaron J. O. Lewis, Robert J. Keenan, Ramanujan S. Hegde
Summary: This study provides insights into the biogenesis of multipass membrane proteins, revealing that the nascent chain is not engaged with Sec61 but is occluded and closed by CCDC47. Asterix redirects the substrate to a location behind Sec61, where the PAT complex contributes to the formation of a semi-enclosed cavity for the insertion and folding of multipass proteins.
Article
Multidisciplinary Sciences
Yong Xue, Jiang-Guo Meng, Peng-Fei Jia, Zheng-Rong Zhang, Hong-Ju Li, Wei-Cai Yang
Summary: This study reports a mechanism for the sorting of cell surface receptors by three ER membrane localized proteins. The mechanism is crucial for the proper sorting of leucine-rich repeat receptor kinases (LRR-RKs) to the plasma membrane.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Sarah O'Keefe, Peristera Roboti, Kwabena B. Duah, Guanghui Zong, Hayden Schneider, Wei Q. Shi, Stephen High
Summary: The study found that the small molecule inhibitor Ipom-F can effectively block the synthesis of SARS-CoV-2 infection proteins to reduce pathogenicity, suggesting a new strategy for antiviral drugs.
JOURNAL OF CELL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Martin Jung, Richard Zimmermann
Summary: Through quantitative mass spectrometry analysis, the redundancy in the components for the targeting and insertion of membrane proteins into the endoplasmic reticulum (ER) was studied. Different signal peptide sequences were found to affect the targeting and insertion of membrane proteins, and some auxiliary components were found to share similar client spectra with the Sec61 complex.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sanaz Dastghaib, P. Sravan Kumar, Sajjad Aftabi, Gautam Damera, Azadeh Dalvand, Adel Sepanjnia, Mohammad Kiumarsi, Mohamad-Reza Aghanoori, Sukhwinder Singh Sohal, Sudharsana R. Ande, Javad Alizadeh, Pooneh Mokarram, Saeid Ghavami, Pawan Sharma, Amir A. Zeki
Summary: Lung cells are exposed to internal and external stressors, leading to disruption of protein homeostasis and activation of the UPR. Dysregulation of the UPR is associated with disease development and various human conditions. Compounds targeting the UPR pathway show potential for future therapeutic interventions.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Genetics & Heredity
Jiancheng Sun, Feng Qin, Fuzhen Sun, Ping He, Erjun Wei, Runpeng Wang, Feng Zhu, Qiang Wang, Xudong Tang, Yiling Zhang, Zhongyuan Shen
Summary: In this study, the NbSec61 alpha and NbSec61 gamma genes were identified in the microsporidian Nosema bombycis for the first time. These genes were found to play important roles in the transport across the endoplasmic reticulum and intracellular development of N. bombycis.
Article
Biochemistry & Molecular Biology
Patricia Franzka, Svenja Caren Schueler, Takfarinas Kentache, Robert Storm, Andrea Bock, Istvan Katona, Joachim Weis, Katrin Buder, Christoph Kaether, Christian A. Hubner
Summary: Proteins of the secretory pathway undergo glycosylation in the ER and Golgi apparatus. Mutations in GMPPA can cause AAMR syndrome with various symptoms. Loss of GMPPA leads to Golgi fragmentation, altered protein abundance, reduced furin activity, and increased retention of alpha-DG.
Article
Plant Sciences
Tian Pan, Yihua Wang, Ruonan Jing, Yongfei Wang, Zhongyan Wei, Binglei Zhang, Cailin Lei, Yanzhou Qi, Fan Wang, Xiuhao Bao, Mengyuan Yan, Yu Zhang, Pengcheng Zhang, Mingzhou Yu, Gexing Wan, Yu Chen, Wenkun Yang, Jianping Zhu, Yun Zhu, Shanshan Zhu, Zhijun Cheng, Xin Zhang, Ling Jiang, Yulong Ren, Jianmin Wan
Summary: Protein storage vacuoles (PSVs) in plant seeds accumulate storage proteins, and the study of the rice gpa7 mutant revealed abnormalities in protein targeting and trafficking pathways related to Rab5 and Rab7. The mutant, with altered CCZ1 function, displayed mistargeting of glutelins and abnormal accumulation of storage compartment-like structures. The findings suggest the involvement of the MON1-CCZ1 complex in post-Golgi trafficking of rice storage proteins.
Letter
Clinical Neurology
Keun-Tae Kim, Sun-Uk Lee, Ileok Jung, Jung Bin Kim, Sungwook Yu, Ji-Soo Kim
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Soni Shankhwar, Karin Schwarz, Rashmi Katiyar, Martin Jung, Stephan Maxeiner, Thomas C. Suedhof, Frank Schmitz
Summary: In this study, we investigated the essential role of the RIBEYE B-domain in the assembly of synaptic ribbons. Our results demonstrate that the B-domain is necessary for the assembly of RIBEYE into synaptic ribbons, providing further evidence that RIBEYE is the central organizer of these structures.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biology
Mark Sicking, Martina Zivna, Pratiti Bhadra, Veronika Baresova, Andrea Tirincsi, Drazena Hadzibeganovic, Katerina Hodanova, Petr Vyletal, Jana Sovova, Ivana Jedlickova, Martin Jung, Thomas Bell, Volkhard Helms, Anthony J. Bleyer, Stanislav Kmoch, Adolfo Cavalie, Sven Lang
Summary: The idiopathic SEC61A1 missense mutations have been found to cause a localized kidney disease by impairing protein transport and calcium ion homeostasis. Treatment with the molecular chaperone phenylbutyrate can reverse these defects.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell Biology
Jialin Zhou, Martin Jung, Kai S. Dimmer, Doron Rapaport
Summary: In this study, we investigated the biogenesis of multi-span proteins in the mitochondrial outer membrane. Our findings suggest that the targeting specificity and efficiency of these proteins are influenced by their length, as well as the behavior of the membrane. Additionally, cytosolic proteins do not significantly contribute to the biogenesis process.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Chemistry, Physical
Nicolas Kuenzel, Volkhard Helms
Summary: PDZ domains form a large family of adaptor proteins that bind to the C-terminal tails of their binding partner proteins. This study used molecular dynamics simulations and alchemical free energy calculations to investigate the binding of different peptide sequences to PDZ domains. The simulations accurately reproduced the known binding characteristics and revealed the importance of specific amino acid residues in the binding process. However, there were some inaccuracies in predicting the binding of phosphorylated peptides, which differed from experimental results.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Genetics & Heredity
Klaudia K. Maruszczak, Martin Jung, Shafqat Rasool, Jean-Francois Trempe, Doron Rapaport
Summary: Mitochondria dysfunction is involved in the pathomechanism of various diseases, including Parkinson's disease. PINK1, a key component involved in the degradation of damaged mitochondria by mitophagy, relies heavily on the import receptor TOM70 for its association with mitochondria. This study also reveals the moderate role of TOM7 in the association of PINK1 with the TOM complex. The TOM40 pore lumen is crucial for PINK1's stable interaction with the TOM complex and further association with the mitochondrial outer membrane (MOM).
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Biochemistry & Molecular Biology
Shweta Suiwal, Mayur Dembla, Karin Schwarz, Rashmi Katiyar, Martin Jung, Yvonne Carius, Stephan Maxeiner, Marcel A. Lauterbach, C. Roy D. Lancaster, Frank Schmitz
Summary: Unc119 protein mediates transport of myristoylated proteins to the photoreceptor outer segment and is also enriched in photoreceptor synapses. The synaptic ribbon could be involved in the discharge of Unc119-bound lipid-modified proteins. Proteins associated with Unc119 may play important roles in photoreceptor synapses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sarah O'Keefe, Pratiti Bhadra, Kwabena B. Duah, Guanghui Zong, Levise Tenay, Lauren Andrews, Hayden Schneider, Ashley Anderson, Zhijian Hu, Hazim S. Aljewari, Belinda S. Hall, Rachel E. Simmonds, Volkhard Helms, Stephen High, Wei Q. Shi
Summary: This study demonstrates that macrocyclic integrity is not necessary for the cytotoxic inhibition of Sec61-dependent protein translocation by Ipom-F. The researchers find that open-chain analogues can interact with multiple sites on the Sec61 alpha subunit. Additionally, they discover a stereochemically simplified analogue that is more potent and easier to synthesize.
Review
Physiology
Sven Lang, Duy Nguyen, Pratiti Bhadra, Martin Jung, Volkhard Helms, Richard Zimmermann
Summary: Approximately 30% of polypeptides enter the secretory pathway in human cells, and this process involves various signal peptides and transmembrane helices. Most precursor polypeptides are integrated into or translocated across the ER membrane via the Sec61 channel, but certain precursor polypeptides require specific auxiliary components for gating. Recent studies have provided insights into the client spectrum and specificities of some auxiliary components. By combining siRNA-mediated depletion with quantitative proteomics, we can determine the preference of certain pathways or components in intact human cells.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Alina Dittrich, Girish Ramesh, Martin Jung, Frank Schmitz
Summary: This study demonstrates the localization of rabconnectin-3a (RC3a), also known as Dmx-like 2 (DMXL2), to the synaptic ribbons of rod photoreceptor synapses in the mouse retina, suggesting its role in ensuring reliable synaptic communication.
Article
Biochemistry & Molecular Biology
Colya N. Englisch, Jakob Steinhaeuser, Silke Wemmert, Martin Jung, Joshua Gawlitza, Gentiana Wenzel, Bernhard Schick, Thomas Tschernig
Summary: This study aimed to detect the expression of TRPC6, TRPC5, and TRPC3 in the human cochlea. Temporal bone pairs were excised from ten body donors, assessed using computed tomography scans, decalcified using 20% EDTA solutions, and subjected to immunohistochemistry with knockout-tested antibodies. Specific staining was observed in the organ of Corti, the stria vascularis, the spiral lamina, the spiral ganglion neurons, and the cochlear nerves. This unique report supports the hypothesis of the potentially critical role of TRPC channels in human cochlear health and disease, as suggested in previous rodent experiments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Martin Jung, Richard Zimmermann
Summary: Through quantitative mass spectrometry analysis, the redundancy in the components for the targeting and insertion of membrane proteins into the endoplasmic reticulum (ER) was studied. Different signal peptide sequences were found to affect the targeting and insertion of membrane proteins, and some auxiliary components were found to share similar client spectra with the Sec61 complex.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Chethan K. Krishna, Nadine Schmidt, Bettina G. Tippler, Wolfgang Schliebs, Martin Jung, Konstanze F. Winklhofer, Ralf Erdmann, Vishal C. Kalel
Summary: This study characterized the PEX19 binding sites of PEX11 in Trypanosoma brucei and Saccharomyces cerevisiae. PEX11 contains two binding sites, one at the N-terminus and a second near the first transmembrane domain. These binding sites are essential for maintaining steady-state concentration and efficient targeting to peroxisomes and glycosomes, and mutations result in protein mislocalization to mitochondria.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Meeting Abstract
Oncology
Julia S. M. Zimmermann, Annika Cullmann, Askin Kaya, Merle Doerk, Maximilian Linxweiler, Marc P. Radosa, Sven Lang, Martin Jung, Erich F. Solomayer, Julia C. Radosa
Article
Medicine, Research & Experimental
Moritz-Valentin Schreck, Caroline Burgard, Alexander Schmidtke, Ina Hierlmeier, Tobias Stemler, Stephan Maus, Florian Rosar, Martin Jung, Andreas Speicher, Samer Ezziddin, Jason P. Holland, Mark D. Bartholomae
Summary: The study developed a novel GRPr antagonistic probe using a metal chelator that forms positively charged metal complexes. The results showed that the metal-labeled conjugate had high affinity similar to a potent antagonist. Small-animal PET imaging demonstrated high radioactivity accumulation in GRPr-expressing tumors and pancreas. The probe successfully visualized an estrogen receptor-positive tumor in a breast cancer patient.
MOLECULAR PHARMACEUTICS
(2023)
