Article
Cell Biology
Bing-Ru Yan, Taoyingnan Li, Etienne Coyaud, Estelle M. N. Laurent, Jonathan St-Germain, Yuhuan Zhou, Peter K. Kim, Brian Raught, John H. Brumell
Summary: The protein C5orf51 plays a crucial role in regulating the activity of RAB7A during mitophagy, facilitating the shuttle of RAB7A between late endosomes and mitochondria. Depletion of C5orf51 leads to compromised localization of RAB7A on depolarized mitochondria, degradation by the proteasome, and inhibition of ATG9A recruitment to depolarized mitochondria.
Article
Biochemistry & Molecular Biology
Aaron M. N. Joiner, Ben P. Phillips, Kumar Yugandhar, Ethan J. Sanford, Marcus B. Smolka, Haiyuan Yu, Elizabeth A. Miller, J. Christopher Fromme
Summary: The study revealed the regulation of Rab1 activation by the TRAPPIII complex, with the Trs85 subunit serving as a membrane anchor for the entire complex via its amphipathic helix. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.
Editorial Material
Biochemistry & Molecular Biology
Jianjun Duan, David G. Lambright
Summary: The article explores the structural basis for Sar1 activation by the Sec12 guanine nucleotide exchange factor during COPII vesicle biogenesis at the endoplasmic reticulum.
Article
Multidisciplinary Sciences
Xin Yong, Guowen Jia, Zhe Liu, Chunzhuang Zhou, Jiamin Yi, Li Chen, Lu Chen, Yuan Wang, Qingxiang Sun, Daniel D. Billadeau, Zhaoming Su, Da Jia
Summary: In this study, the structure of the Drosophila Mon1-Ccz1-RMC1 complex was determined using cryogenic-electron microscopy. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1, explaining the binding specificity of the complex. The assembly of RMC1 with Mon1-Ccz1 is required for cellular RAB7A activation, autophagic functions, and organismal development in zebrafish.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Rahul Kumar, Vincent Francis, Maria S. Ioannou, Adriana Aguila, Maleeha Khan, Emily Banks, Gopinath Kulasekaran, Peter S. McPherson
Summary: Cytokinesis is regulated by Rab proteins and guanine nucleotide exchange factors (GEFs). DENND2B, a protein associated with cancer and congenital disorders, acts as a GEF for Rab35 and plays a crucial role in cytokinetic abscission. Knockdown of DENND2B impairs actin depolymerization, delays abscission, and activates checkpoint proteins, leading to multinucleated cells and altered cytokinesis.
Article
Chemistry, Analytical
Jiarong Wang, Bo Wu, Youjia Zhang, Liang Ge, Junfeng Wang
Summary: In this study, a 1D F-19 NMR-based method was developed for rapid detection of GEF activity of sGTPases, by tracking the conformational changes of the Arf6 switch region. This strategy could potentially be applied to monitor the conformational change of Arf6 or other sGTPase and detect the activities of sGTPase regulatory proteins in physiology and pathology environments.
ANALYTICAL CHEMISTRY
(2022)
Article
Cell Biology
Justyna M. Meissner, Katarina Akhmetova, Tomasz Szul, Ekaterina G. Viktorova, Bingdong Sha, Jay M. Bhatt, Eunjoo J. Lee, Richard A. Kahn, George A. Belov, Igor Chesnokov, Elizabeth Sztul
Summary: In this study, we identified the essential role of the HDS3 domain in GBF1 membrane association in mammalian cells and its critical function during Drosophila melanogaster development. We characterized the interdomain arrangements of GBF1 by electron microscopy and proposed models for GBF1 engagement on the membrane.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Agronomy
Munsif Ali Shad, Yixian Wang, Hui Zhang, Shanshan Zhai, Abdullah Shalmani, Yibo Li
Summary: Using in-silico analysis and transgenic approaches, the evolutionary relationships and functions of GEF and GDI genes in rice were dissected. These genes were highly expressed in panicles, hulls, and stamens. They interacted with grain-size protein GS3, playing a crucial role in the regulation of grain size and plant architecture.
Article
Cell Biology
Zhuofu Ni, Xiaodong Cheng
Summary: EPAC proteins are only present in multicellular Metazoa, with EPAC1 only associated with chordates and EPAC2 spanning the entire animal kingdom. EPAC1 has undergone more selection and evolved faster than EPAC2.
Article
Oncology
Xin Zhang, Liangliang Ren, Junhua Wu, Rongni Feng, Yunyang Chen, Ronggang Li, Meimei Wu, Mingzhu Zheng, Xing Gui Wu, Wanjun Luo, Hongle He, Yanming Huang, Miaoling Tang, Jun Li
Summary: ARHGEF37 is upregulated in HCC and associated with tumor invasiveness, pulmonary metastasis and poor prognosis. Overexpression of ARHGEF37 enhances HCC cell extravasation and metastasis by promoting cell adhesion and migration. ARHGEF37 activates Cdc42 to promote invadopodia formation in HCC cells, disrupting the interaction between endothelial cells and pericytes.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Arun A. Chandrakumar, Etienne Coyaud, Christopher B. Marshall, Mitsuhiko Ikura, Brian Raught, Robert Rottapel
Summary: Rab11 GTPase proteins play important roles in cytokinesis, ciliogenesis, and lumenogenesis; SH3BP5 and SH3BP5L are crucial for the activation of Rab11a and cyst lumen formation; Tankyrase regulates epithelial polarity and lumen formation by inhibiting SH3BP5 and SH3BP5L, which is counteracted by RNF146.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Cell Biology
Sana Abdul Khaliq, Zobia Umair, Mee-Sup Yoon
Summary: ARHGEF3 is a selective guanine nucleotide exchange factor that activates RhoA and RhoB and inhibits mTORC2 and Akt. It is also involved in autophagy-related muscle pathologies and plays roles in controlling bone mineral density, platelet formation and differentiation, and Hirschsprung disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rahul Kumar, Vincent Francis, Gopinath Kulasekaran, Maleeha Khan, Gary A. B. Armstrong, Peter S. McPherson
Summary: This study reveals unexpected diversity in DENN domain-mediated activation of Rabs, identifies a previously unidentified non-Rab substrate for a DENN domain, and discovers a new regulatory protein in primary ciliogenesis.
Article
Biochemistry & Molecular Biology
Andreas Boland, Jean-Francois Cote, David Barford
Summary: DOCK proteins are a type of guanine nucleotide exchange factors (GEFs) that activate CDC42 and RAC1 to regulate cellular processes. They have a catalytic DHR2 domain and a DHR1 domain that targets them to plasma membranes. Different subfamilies of DOCK GEFs activate CDC42 and RAC1 with specificities and are regulated by accessory signaling domains and ELMO proteins. Structural studies have provided insights into the mechanism of DOCK proteins, which are involved in various diseases and need to be further understood for targeted therapy.
Article
Biochemistry & Molecular Biology
Tong Li, Juan Du, Mingfa Ren
Summary: Ab initio modeling was used to study the interaction between His73 and Gly158, and the results showed that the methylation of His73 contributes to the structural stability of actin and restricts the material exchange pathway in F-actin dynamics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Kalle Gehring, Veronique Sauve, George Sung, Guennadi Kozlov
Review
Biochemistry & Molecular Biology
Guennadi Kozlov, Kalle Gehring
Editorial Material
Oncology
Kalle Gehring, Hiroaki Miki
Summary: Phosphatases of regenerating liver (PRL1-3) are highly oncogenic protein phosphatases, but their mechanism of action remains poorly understood. Recent identification of a catalytically inactive PRL mutant that retains oncogenicity in a mouse model offers promise to clarify whether PRLs function as phosphatases or pseudo-phosphatases in different cancer models.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Sandy Mattijssen, Guennadi Kozlov, Sergei Gaidamakov, Amitabh Ranjan, Bruno D. Fonseca, Kalle Gehring, Richard J. Maraia
Summary: The La-module, consisting of a La motif (LaM), a linker, and an RNA recognition motif (RRM), is present in several La-related proteins with distinct activities in RNA metabolism. La protein and LARP7's La-modules protect nuclear RNAs with UUU-3MODIFIER LETTER PRIME tails, while LARP4 stabilizes mRNA by binding poly(A) and PABPC1. LARP1, with a PAM2 motif, exhibits similar activities mediated by its La-module, providing poly(A) protection and stabilization to mRNAs.
Correction
Oncology
Kalle Gehring, Hiroaki Miki
BRITISH JOURNAL OF CANCER
(2021)
Review
Biochemistry & Molecular Biology
Sandy Mattijssen, Guennadi Kozlov, Bruno D. Fonseca, Kalle Gehring, Richard J. Maraia
Summary: La and LARP7 are involved in RNA 3’ end binding and protection, while LARP1 and LARP4 mainly interact with poly(A) and PABP, protecting mRNA poly(A) tails from deadenylases.
Article
Multidisciplinary Sciences
Yu Seby Chen, Guennadi Kozlov, Brandon E. Moeller, Ahmed Rohaim, Rayan Fakih, Benoit Roux, John E. Burke, Kalle Gehring
Summary: CNNM/CorB proteins are a family of membrane proteins associated with Mg2+ transport. Structural studies on an archaeal CorB protein in apo state and with Mg2+-ATP bound, along with biophysical experiments, suggest the direct transport of Mg2+ by CorB proteins.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Kalle Gehring, Guennadi Kozlov, Meng Yang, Rayan Fakih
Summary: Phosphatases of regenerating liver (PRLs) are protein phosphatases involved in the control of cell growth and migration. Recent studies have shown that PRLs have dual functions as both catalytically active enzymes and pseudophosphatases, contributing to their unique properties.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Marta Vranas, Yang Lu, Shafqat Rasool, Nathalie Croteau, Jonathan D. Krett, Veronique Sauve, Kalle Gehring, Edward A. Fon, Thomas M. Durcan, Jean-Francois Trempe
Summary: Mutations in Parkin and PINK1 cause early-onset familial Parkinson's disease. The study found that His433 contributes to the catalysis of Parkin and its mutation impairs mitophagy. Mfn2 is a kinetically preferred substrate for Parkin, co-localizing with PINK1 and phospho-ubiquitin upon mitochondrial depolarization.
Article
Biochemistry & Molecular Biology
Veronique Sauve, George Sung, Emma J. MacDougall, Guennadi Kozlov, Anshu Saran, Rayan Fakih, Edward A. Fon, Kalle Gehring
Summary: PINK1 and parkin play a crucial role in mitochondrial quality control and are often mutated in Parkinson's disease. PINK1 phosphorylates ubiquitin and the Ubl domain of parkin to regulate the localization and activity of parkin. The study discovered that phospho-ubiquitin can bind to two different sites on parkin, controlling its localization and releasing its autoinhibition. Activation of parkin by phosphorylated ubiquitin plays a significant role in the PINK1-parkin pathway.
Article
Multidisciplinary Sciences
Sharon Kaisari, Shirly Miniowitz-Shemtov, Danielle Sitry-Shevah, Pnina Shomer, Guennadi Kozlov, Kalle Gehring, Avram Hershko
Summary: The mitotic checkpoint system ensures accurate chromosome segregation in mitosis. UBR5 is a protein associated with mitotic checkpoint proteins and plays a role in regulating the inactivation of the mitotic checkpoint.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Cell Biology
Rayan Fakih, Veronique Sauve, Kalle Gehring
Summary: Parkinson's disease is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Mutations in PRKN and PINK1 genes are responsible for early onset Parkinson's. Our research shows that PINK1 can activate PRKN to promote mitophagy. This signaling pathway offers potential for the development of therapeutics.
Article
Biochemistry & Molecular Biology
Rayan Fakih, Veronique Sauve, Kalle Gehring
Summary: Parkin and PINK1 regulate a mitochondrial quality control system that is mutated in some early onset forms of Parkinson's disease. Recently, an alternative feed-forward mechanism was identified that bypasses the need for parkin phosphorylation. This study reveals the structure of parkin activated through this feed-forward mechanism and provides insights into the differences in specificity and affinity of the binding sites.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Yu Seby Chen, Kalle Gehring
Summary: Magnesium (Mg2+) is a vital divalent cation in cells and has crucial roles in various biological processes. CNNMs, a class of Mg2+ transporters, were initially found in bacteria and are present in humans as four proteins, involved in divalent cation transport, genetic diseases, and cancer. Eukaryotic CNNMs consist of four domains, including an extracellular domain, a transmembrane domain, a CBS-pair domain, and a cyclic nucleotide-binding homology domain. This review focuses on the structural and functional studies of eukaryotic and prokaryotic CNNMs, which contribute to the understanding of their regulation and ion transport mechanism. Recent studies on prokaryotic CNNMs show that the transmembrane domain facilitates ion transport, while the CBS-pair domain may regulate the process through binding divalent cations. Moreover, studies on mammalian CNNMs have revealed new binding partners, leading to better comprehension of this widely conserved family of ion transporters.
Article
Biochemistry & Molecular Biology
Rayan Fakih, Robert H. Goldstein, Guennadi Kozlov, Kalle Gehring
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)