Review
Chemistry, Medicinal
Hye-Won Shin, Hiroyuki Takatsu
Summary: This article reviews the current understanding of the regulatory mechanism of P4-ATPase activity and localization in mammalian cells, while also mentioning the remaining unknowns in this field.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Biochemistry & Molecular Biology
Francesco Tadini-Buoninsegni, Stine A. Mikkelsen, Louise S. Mogensen, Rikke Holm, Robert S. Molday, Jens Peter Andersen
Summary: The study reveals the electrogenicity of ATP8A2 and its potential phospholipid translocation pathway involving residues with positively charged side chains.
Article
Biochemistry & Molecular Biology
Yuta Yamazaki, Keiko Kono
Summary: This study reveals that clathrin-mediated trafficking of phospholipid flippases is critical for the recruitment of the exocyst complex to the damage site during plasma membrane/cell wall repair in budding yeast.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Sankalp Shukla, Tobias Baumgart
Summary: The eukaryotic plasma membrane exhibits crucial asymmetry maintained by translocases, impacting cellular processes, with recent advances in understanding flippase mechanisms and their potential coupling to membrane curvature. Studies on lipid flippases have increased significantly, providing insights into their functional mechanisms and interactions with membrane shape, shaping potential future directions in the field.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Biochemistry & Molecular Biology
Kai Chen, Ozlem Gunay-Esiyok, Melissa Klingeberg, Stephan Marquardt, Thomas Guenther Pomorski, Nishith Gupta
Summary: By studying Toxoplasma gondii, it was found that the parasite can salvage phosphatidylserine and phosphatidylethanolamine from its environment but not phosphatidylcholine, implying the significance of exogenous lipids in membrane biogenesis of the parasite.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Immunology
Anais Lamy, Ewerton Macarini-Bruzaferro, Thibaud Dieudonne, Alex Peralvarez-Marin, Guillaume Lenoir, Cedric Montigny, Marc le Maire, Jose Luis Vazquez-Ibar
Summary: Gene targeting approaches have highlighted the essential role of membrane transport proteins in lipid transport and maintenance of lipid asymmetry in the malaria parasite. Specifically, ATP2 has been identified as a crucial target for potential antimalarial drugs. The study reveals that PcATP2 interacts with Plasmodium-encoded Cdc50 proteins and shows ATPase activity in the presence of phospholipids.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Plant Sciences
Rosa L. Lopez-Marques, James A. Davis, Jeffrey F. Harper, Michael Palmgren
Summary: The lipid bilayer of biological membranes is complex and asymmetric, with protein P4 ATPase playing a role in generating this asymmetry. Arabidopsis contains 12 P4 ATPases, with studies confirming their essential role in basal cellular functions.
Review
Cell Biology
Guillaume Lenoir, Juan Martin D'Ambrosio, Thibaud Dieudonne, Alenka Copic
Summary: The distribution of PS within cellular membranes is controlled by a variety of factors, including PS biosynthesis enzymes, lipid transfer proteins, and lipid flippases. The enrichment of PS in specific compartments requires energy input, and PS transfer may be achieved by passive flow. The presence of lateral PS nanodomains can alter the steepness or direction of PS gradients between different compartments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Dawei Guo, Himansha Singh, Atsushi Shimoyama, Charlotte Guffick, Yakun Tang, Sam M. Rowe, Timothy Noel, David R. Spring, Koichi Fukase, Hendrik W. van Veen
Summary: The study reveals that the energetics of lipid transport by the ABC transporter MsbA is dependent on the type of lipid, with varying dependencies on ATP and chemical proton gradient for different types of lipids.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Jinkun Xu, Yilin He, Xiaofei Wu, Long Li
Summary: This study reports the cryoelectron microscopy structures of a yeast PC-flipping P4-ATPase, revealing that its conformational state is regulated by lipid composition. In native membranes, the enzyme may stay in an inactive conformation that cannot support lipid translocation.
Article
Multidisciplinary Sciences
Meng-Ting Cheng, Yu Chen, Zhi-Peng Chen, Xin Liu, Zhiyong Zhang, Yuxing Chen, Wen-Tao Hou, Cong-Zhao Zhou
Summary: The study discovered the auto-inhibited state of ATP8B1 and its activation upon substrate binding. These findings are not only significant for understanding the mechanism of ATP8B1-mediated restoration of human membrane lipid asymmetry, but also advance our understanding of the molecular mechanism of P4 ATPases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ian J. Roney, David Z. Rudner
Summary: Sorting of phospholipids between membrane bilayers is a fundamental problem, and the enzymes that catalyze phospholipid reorientation in bacteria remain unknown. Members of the DedA superfamily have been implicated in lipid carrier transport and lipid scrambling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Geok-Lin Chua, Bryan C. Tan, Randy Y. J. Loke, Menglan He, Cheen-Fei Chin, Bernice H. Wong, Alvin C. Y. Kuk, Mei Ding, Markus R. Wenk, Lan Guan, Federico Torta, David L. Silver
Summary: Mfsd2a is a sodium-dependent lysophosphatidylcholine transporter expressed at the blood-brain barrier that is crucial for omega-3 fatty acid transport and brain development. Although the transport mechanism of Mfsd2a has been proposed through cryo-EM structures, the biochem-ical evidence of flippase activity and sodium-dependent LPC inversion is still lacking. In this study, an in vitro assay using recombinant Mfsd2a reconstituted in liposomes was established to demonstrate the flipping of lysophosphatidylserine (LPS) from the outer to the inner leaflet of a membrane bilayer in a sodium-dependent manner. Through cryo-EM structures, mutagenesis, and cell-based transport assay, amino acid residues important for Mfsd2a activity were identified, providing direct biochemical evidence of Mfsd2a functioning as a lysolipid flippase.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Ping Li, Kaituo Wang, Nina Salustros, Christina Gronberg, Pontus Gourdon
Summary: In this study, cryo-EM structures of a yeast homolog of human ATP13A2-5, Ypk9, were used to depict three separate transport cycle intermediates, including spermine-bound conformations. The findings suggest a shared principle of transport and regulation among evolutionary related P4-, P5A- and P5B-ATPases, providing insights for the analysis of associated disorders such as Parkinson's disease.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Eugenia M. Yazlovitskaya, Todd R. Graham
Summary: Lipids are crucial for cellular functions and play a significant role in cancer development and progression. Type IV P-type ATPases, known as flippases, regulate membrane lipid asymmetry and are closely associated with cancer-related lipid changes. Recent studies have focused on the role of flippases, particularly P4-ATPases, in cancer and their potential as therapeutic targets.
Article
Biochemistry & Molecular Biology
Xiaoming Zhou, Tessy T. Sebastian, Todd R. Graham
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Multidisciplinary Sciences
Xiaoming Zhou, Elena J. Levin, Yaping Pan, Jason G. McCoy, Ruchika Sharma, Brian Kloss, Renato Bruni, Matthias Quick, Ming Zhou
Article
Multidisciplinary Sciences
Xiaoming Zhou, Todd R. Graham
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2009)
Article
Biochemical Research Methods
Xiaodong Wang, Ying Lyu, Yujia Ji, Ziyi Sun, Xiaoming Zhou
Summary: Research suggests that the apical sodium-dependent bile acid transporter utilizes an elevator-style alternating-access model for bile acid transport. A new crystal structure similar to an existing PDB entry was obtained through engineering, supporting the hypothesis that the structure represents a functional outward-facing conformation of the transporter.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Xiaodong Wang, Ying Lyu, Yujia Ji, Ziyi Sun, Xiaoming Zhou
Summary: This study combines molecular docking, structure determination, and functional analysis to define and validate the details of substrate binding in ASBT(Yf), providing coherent evidence for a clearer understanding of how the substrate binds in the central cavity of ASBT(Yf) in line with the alternating-access model.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Fuhui Meng, Yang Xiao, Yujia Ji, Ziyi Sun, Xiaoming Zhou
Summary: This study provides structural and functional evidence for the likely ligand entry pathway of sigma 1R, a nonopioid transmembrane receptor implicated in various diseases. By analyzing crystal structures of sigma R-1 from Xenopus laevis, the authors suggest that protein conformational changes involving the carboxy-terminal two-helix bundle may be responsible for ligand binding site access.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Senfeng Zhang, Chunting Fu, Yongbo Luo, Qingrong Xie, Tong Xu, Ziyi Sun, Zhaoming Su, Xiaoming Zhou
Summary: Zinc transporter 8 plays an important role in the transport of zinc ions into the lumen of insulin secretory granules. This study reveals the mechanistic role of protons in disrupting the coordination geometry of the transmembrane zinc-binding site, facilitating the release of zinc ions.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Xiaodong Wang, Yuwei Yang, Ziyi Sun, Xiaoming Zhou
Summary: This study presents the crystal structure of the M protein from Pipistrellus bat coronavirus HKU5, which is closely related to MERS-CoV, SARS-CoV, and SARS-CoV-2 M proteins. The interaction analysis indicates that the carboxy-terminus of the batCOV5 nucleocapsid protein mediates its interaction with batCOV5-M. A computational docking analysis proposes an M-N interaction model, providing insight into the mechanism of M protein-mediated protein interactions.
Article
Biochemistry & Molecular Biology
Jianjun Fan, Yang Xiao, Matthias Quick, Yuwei Yang, Ziyi Sun, Jonathan A. Javitch, Xiaoming Zhou
Summary: The neurotransmitter:sodium symporter (NSS) homolog LeuT from Aquifex aeolicus is a valuable model for studying the transport mechanism of the NSS family. Crystal structures and studies on substrate binding dynamics suggest a potential competition between outward-open and outward-occluded states during substrate transport. The interplay between the protonation state of Glu290 and Na1 binding may regulate the outward-open-to-occluded transition.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Chenchen Bian, Xiangtong Yuan, Caihong Zeng, Jian Sun, Gen Kaneko, Hong Ji
Summary: This study investigated the mechanism of docosahexaenoic acid (DHA)-induced apoptosis mediated by mitophagy, using grass carp as an animal model. The results showed that inhibition of mitophagy alleviated apoptosis and eliminated the inhibition of lipid accumulation induced by DHA. Mechanistically, DHA induced mitophagy by activating the PPAR gamma-LC3-BNIP3 pathway. Inhibition of PPAR gamma decreased autophagy-related gene expression and prevented BNIP3/NIX-mediated mitophagy-induced apoptosis, thereby alleviating the inhibition of lipid accumulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Venkatesan Ramya, Karuppiah Prakash Shyam, Arulanandu Angelmary, Balamuthu Kadalmani
Summary: This study reveals that Lauric acid (LA) exerts an epigenetic regulation and metabolic reprogramming on SH-SY5Y neuroblastoma cells through modulation of lncRNA HOTAIR, remodeling of chromatin H3K4 tri-methylation and regulation of glucose uptake by controlling NF-kappa B activation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Sreelekshmi Sreekumar, Karyath Palliyath Gangaraj, Manikantan Syamala Kiran
Summary: This study investigates the intricate interplay between angiogenic regulation and the browning of white adipocytes. The findings reveal that concurrent activation of angiogenesis is necessary for inducing browning of white adipocytes. The study also highlights the role of Vascular endothelial growth factor (VEGF) in promoting angiogenesis and triggering the browning process through the activation of Estrogen receptor alpha (ER alpha) signaling pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Zanxia Cao, Liling Zhao, Mingcui Chen, Zhihong Shi, Lei Liu
Summary: This study investigated the translocation process of cholesterol/calcitriol in bacterial membranes and their effects on membrane structure. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. These findings contribute to a better understanding of the relationship between cholesterol/calcitriol concentrations, lipid bilayer structure, and water permeation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Xiaozhen Guo, Jiawen Wang, Hualing Xu, Yangyang Wang, Yutang Cao, Yingquan Wen, Jiaqi Li, Yameng Liu, Kanglong Wang, Jue Wang, Xianchun Zhong, Chuying Sun, Yongxin Zhang, Jingyi Xu, Cuina Li, Pengxiang Mu, Lingyan Xu, Cen Xie
Summary: This study aims to investigate the role of the gut microbiota-bile acid axis in regulating the diurnal rhythms of metabolic homeostasis and assess the impact of obesity on them. The results show that high fat diet feeding and Leptin gene deficiency disrupt the rhythmic patterns of insulin sensitivity and serum total cholesterol levels. The study provides compelling evidence for the association between diurnal rhythm of insulin sensitivity and gut microbiota-bile acid axis, and elucidates the deleterious effects of obesity on gut microbiome-bile acid metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Giuseppe Pepe, Maria Cotugno, Federico Marracino, Luca Capocci, Ludovica Pizzati, Maurizio Forte, Rosita Stanzione, Pamela Scarselli, Alba Di Pardo, Sebastiano Sciarretta, Massimo Volpe, Speranza Rubattu, Vittorio Maglione
Summary: The study found that enzymes involved in sphingolipid metabolism show abnormal expression in the cardiac tissue of hypertensive rat models, which may be related to the susceptibility to cardiac damage.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
