Article
Biochemistry & Molecular Biology
Jiyoon L. Kim, Shifra Ben-Dor, Eden Rosenfeld-Gur, Anthony H. Futerman
Summary: Ceramide, a lipid moiety synthesized by ceramide synthases, is involved in various cellular processes. This study identified a unique C-terminal motif in Ceramide synthases (CerSs), which plays a role in their enzymatic activity and interaction. Deletion of this motif affected the activity of CerS2 in the presence of CerS6, and disrupted the interaction between CerS2 and CerS6. Furthermore, deletion of the motif impacted cellular protein expression and levels of sphingolipid synthesis regulator, ORMDL1.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Gilberto Betancor, Madeleine Bangham, Jun Ki Jeon, Kanisha Shah, Steven Lynham, Jose M. Jimenez-Guardeno, Michael H. Malim
Summary: Phosphorylation of MX2 plays a crucial role in regulating its antiviral activity and determining susceptible viral substrates.
Article
Biochemistry & Molecular Biology
Emilie Aponte, Marie Lafitte, Audrey Sirvent, Valerie Simon, Maud Barbery, Elise Fourgous, Mariano Maffei, Florence Armand, Romain Hamelin, Julie Pannequin, Philippe Fort, Miquel Pons, Serge Roche, Yvan Boublik
Summary: This study reveals the important role of the unique domain ULBR in Src tyrosine kinase in malignant cell transformation. The ULBR is involved in membrane anchoring, MAPK signaling, and phosphorylation of specific membrane-localized tyrosine kinases needed for Src oncogenic signaling.
News Item
Biochemistry & Molecular Biology
Rasmus Kock Flygaard, Caroline Neumann, Joseph Anthony Lyons, Poul Nissen
Summary: The study reveals the cryo-EM structures of human KCC1 and KCC3b, detailing how regulation by phosphorylation inhibits ion transport activity. The authors also identify a stabilizing binding site for nucleotides and speculate on its functional role.
Article
Chemistry, Physical
Aparna G. Nair, D. Sravanakumar Perumalla, Padmesh Anjukandi
Summary: This study investigates the possibility of generating an internal nucleophile near the active site of nDsbD, identifying Tyr(42)O(-) as a potential nucleophile for cleaving the S-S bond. The research also reveals communication between Tyr(42)O(-) and Asp(68)OH through a water wire, modulating nucleophile formation. The findings suggest a role for solvent in regulating internal nucleophilic reactions and self-activation of nDsbD, which could be important in designing enzyme-targeted inhibitor compounds.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Sijia Bao, Chao Xu
Summary: SETD1A and SETD1B, originating from yeast Set1, the sole H3K4 methyltransferase, have important roles in active gene transcription. Our crystal structures of the RRM domains of human SETD1A and SETD1B reveal their structural differences from the yeast homolog. We found that an intrinsically disordered region in SETD1A/B binds WDR82, and the positively charged regions within human RRM domains might be involved in RNA binding. Our work provides structural insight into the assembly of WDR82 with the catalytic subunits SETD1A/B in the context of the whole complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kento Shimakura, Kai Sato, Shun Mitsui, Suzuka Ono, Asako Otomo, Shinji Hadano
Summary: The results indicate that the intrinsically disordered region (IDR) of ALS2 plays a crucial role in the regulation of intracellular localization and self-oligomerization of ALS2 in cells, while the phosphorylation of certain residues within the IDR has limited effects on such phenotypes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Agricultural Engineering
Jishao Jiang, Yang Wang, Dou Yu, Xing Yao, Jin Han, Ronghui Cheng, Huilin Cui, Guangxuan Yan, Xin Zhang, Guifen Zhu
Summary: This study found that the addition of garbage enzymes during sewage sludge composting increased nitrogen transformation and enzymatic activities, reduced ammonia emissions, and increased total nitrogen content. Microbiological analysis revealed an increase in the relative abundance of Firmicutes with garbage enzyme addition.
BIORESOURCE TECHNOLOGY
(2021)
Article
Cell Biology
Jingyue Jia, Fulong Wang, Zambarlal Bhujabal, Ryan Peters, Michal Mudd, Thabata Duque, Lee Allers, Ruheena Javed, Michelle Salemi, Christian Behrends, Brett Phinney, Terje Johansen, Vojo Deretic
Summary: Lysosomal damage induces the formation of stress granules and coordinates mTOR inactivation through the process of membrane atg8ylation. This process is effective against various lysosomal damaging agents.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhihao Wang, Zhicheng Pan, Samir Adhikari, Bryan T. Harada, Lei Shen, Wei Yuan, Tharindumala Abeywardana, Qais Al-Hadid, Jeremy M. Stark, Chuan He, Lan Lin, Yanzhong Yang
Summary: The research reveals that arginine methylation of METTL14 is a novel pathway controlling m(6)A deposition in mammalian cells, with deficiency in this methylation leading to significantly reduced global m(6)A levels in mESCs. These findings highlight the importance of arginine methylation in RNA metabolism and its impact on various cellular processes, including stem cell maintenance and DNA repair.
Article
Environmental Sciences
Meiqi Chen, Jisheng Xu, Zengqiang Li, Dandan Li, Qingxia Wang, Yunpeng Zhou, Wei Guo, Donghao Ma, Jiabao Zhang, Bingzi Zhao
Summary: This study found that long-term nitrogen fertilization significantly increases the levels of soil acid hydrolyzable nitrogen (AHN) and its fractions, and these changes are mainly caused by specific microbial taxa and enzyme activities. These microbial taxa and enzyme activities are closely related to nitrogen fertilizer input and participate in organic nitrogen degradation and nitrogen-releasing processes. These results provide new insights into the effects of nitrogen fertilizer on the formation of soil organic nitrogen, microbial communities, and enzyme activities.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Chemistry, Multidisciplinary
Tongyao Wei, Jiamei Liu, Can Li, Yi Tan, Ruohan Wei, Jinzheng Wang, Hongxiang Wu, Qingrong Li, Heng Liu, Yubo Tang, Xuechen Li
Summary: HMGB1 is a non-histone chromatin-associated protein that plays a crucial role in inflammation regulation. This study developed a protein semi-synthesis strategy to generate acetylated HMGB1 proteins and revealed that acetylation regulates HMGB1's interaction with heparin and its stability against thrombin.
Review
Biochemistry & Molecular Biology
Goro Kato
Summary: This review discusses the structural and functional aspects of Src protein and its regulatory mechanism. By reviewing nuclear magnetic resonance analyses and recent studies, the authors explore new characteristics and regulatory roles of Src protein. Finally, the new regulatory roles are integrated with the canonical model to elucidate the functions of full-length Src.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Florencia Scochera, Gerardo Zerbetto De Palma, Agustina Canessa Fortuna, Jonathan Chevriau, Roxana Toriano, Gabriela Soto, Ari Zeida, Karina Alleva
Summary: Plant PIP aquaporins are crucial in regulating plant water status, with the loopD being the main pH sensor in PIP pH gating. The last part of the C-terminal domain (CT) in PIP channels, not resolved in crystal structures, plays a significant role in modulating the pH for water transport. Molecular dynamics simulations reveal how CT affects the pH sensing in PIP tetramers, providing insights into the importance of differential residues in PIP1 and PIP2 paralogues.
Article
Biochemistry & Molecular Biology
Yagmur Kan, W. Todd Miller
Summary: The phosphorylation of Ack1 MHR regulates its kinase activity, and this phosphorylation occurs in various cancers, potentially contributing to the dysregulation of Ack1. This finding is significant for understanding the important role of Ack1 in tumor progression.
Article
Biochemistry & Molecular Biology
Honoka Tanno, Takayuki Sassa, Megumi Sawai, Akio Kihara
Summary: Branched-chain fatty acids are important components in the meibum lipids secreted from the meibomian glands. Enzymes such as ELOVL1, ELOVL3, and ELOVL7 are responsible for elongating branched-chain acyl-CoAs. Liquid chromatography-tandem mass spectrometry has revealed the predominance of branched-chain lipids in mouse meibomian glands, demonstrating the significance of ELOVL1 in elongating branched-chain VLC acyl-CoAs in vivo.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Clinical Neurology
Taiko Takahashi, Sevcan Mercan, Takayuki Sassa, Gunseli Bayram Akcapinar, Kanay Yararbas, Seda Susgun, Sibel Aylin Ugur Iseri, Akio Kihara, Nihan Hande Akcakaya
Summary: This study describes two siblings with cerebral palsy caused by an ELOVL1 splice site mutation. The mutation leads to exon skipping and significant changes in the lipid composition of the skin stratum corneum.
BRAIN & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Kento Otsuka, Megumi Sawai-Ogawa, Akio Kihara
Summary: Fatty acyl-CoA reductases (FARs) play a crucial role in the synthesis of meibum lipids, which are important for tear stability and eye health. This study reveals the specific functions of two FAR isozymes (FAR1 and FAR2) in the production of different chain lengths of fatty alcohols (FAls), and highlights the importance of FAl-containing meibum lipids in the formation of a functional tear film lipid layer.
Article
Biochemistry & Molecular Biology
Madoka Suzuki, Yusuke Ohno, Akio Kihara
Summary: This study used LC/MS/MS analysis to identify 1,327 unbound ceramides and 254 protein-bound ceramides in the stratum corneum. The researchers discovered a wide variety of ceramide species with different long-chain bases in the human skin, and demonstrated the production of specific long-chain bases by one of the enzymes. This study provides a molecular basis for understanding ceramide diversity in the skin and the pathogenesis of skin disorders.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Dermatology
Ayami Arai, Takuya Takeichi, Hiroyuki Wakamoto, Takayuki Sassa, Yasutoshi Ito, Yuya Murase, Tomoo Ogi, Masashi Akiyama, Akio Kihara
Summary: Sjogren-Larsson syndrome (SLS) is a neurocutaneous disorder characterized by ichthyosis. This study identified a duplication and a missense mutation in the ALDH3A2 gene of an SLS patient, leading to reduced levels of acylceramides. The findings suggest that the reduction in acylceramide levels may be the primary cause of the ichthyosis symptoms in SLS.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Article
Dermatology
Tomohiro Nohara, Yusuke Ohno, Akio Kihara
Summary: This study validates the involvement of PNPLA1 gene mutations in the pathogenesis of congenital ichthyosis and reveals the correlation between these mutations' effects on acylceramide production and the disease's pathology.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Editorial Material
Ophthalmology
Yuki Hamada, Lena Sasaki, Hikari Uehara, Tomo Suzuki, Shigeru Kinoshita, Kento Otsuka, Akio Kihara, Yoshiaki Yamaguchi, Takahito Miyake, Masao Doi
Article
Biochemistry & Molecular Biology
Satarupa Bhaduri, Analine Aguayo, Yusuke Ohno, Marco Proietto, Jasmine Jung, Isabel Wang, Rachel Kandel, Narinderbir Singh, Ikran Ibrahim, Amit Fulzele, Eric J. Bennett, Akio Kihara, Sonya E. Neal
Summary: This study reveals the association between the pseudoprotease Dfm1 and the SPOTS complex, highlighting their roles in sphingolipid metabolism. Additionally, Dfm1 is found to play a crucial role in the ER export and degradation of Orm2. These findings provide insights into the molecular mechanisms underlying sphingolipid metabolism and its implications in disease.
Article
Cell Biology
Yasuhiro Hirano, Yusuke Ohno, Yoshino Kubota, Tatsuo Fukagawa, Akio Kihara, Tokuko Haraguchi, Yasushi Hiraoka
Summary: Recent studies have revealed that enzymes catalyzing lipid synthesis play a role in maintaining the integrity of the nuclear envelope (NE), but the mechanism involved remains unclear. In this study, the ceramide synthase homolog, Tlc4, was found to suppress NE defects in cells lacking the NE proteins Lem2 and Bqt4. Tlc4, which possesses a conserved TRAM/LAG1/CLN8 domain, functions through its non-catalytic activity and localizes at the NE, endoplasmic reticulum, and cisand medial-Golgi cisternae. The Golgi localization of Tlc4 is closely linked to its activity of suppressing NE defects in the double-deletion mutant of Lem2 and Bqt4.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Takayuki Sassa, Akio Kihara
Summary: The permeability barrier in the oral cavity is crucial for protection against infection. This study reveals the presence of u-O-acylceramides and protein-bound ceramides, which are essential for barrier formation, in the oral mucosae, esophagus, and stomach in mice. Conditional knockout of the fatty acid elongase Elovl1 in the oral mucosae and esophagus leads to increased pigment penetration and enhanced aversive responses. Acylceramides and protein-bound ceramides are also found in human oral mucosae. These findings highlight the importance of acylceramides and protein-bound ceramides in oral barrier formation.
Article
Biochemistry & Molecular Biology
Yuka Tamura, Takayuki Sassa, Takumi Nishizawa, Akio Kihara
Summary: This article mainly discusses spinocerebellar ataxias (SCAs), which are autosomal dominant diseases characterized by cerebellar atrophy and ataxia. It focuses on the SCA34 subtype, which is caused by specific mutations in the ELOVL4 gene. The study shows that these mutations lead to the production of shorter ultra-long-chain polyunsaturated fatty acids (ULC-PCs) in neurons, which may contribute to the pathogenesis and dominant inheritance of SCA34.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Madoka Suzuki, Yusuke Ohno, Akio Kihara
Summary: This study conducted LC/MS/MS analyses to reveal various ceramide species in the human stratum corneum, quantifying a large number of ceramides and providing a molecular basis for understanding the diversity of human skin ceramides and the pathogenesis of skin disorders.
JOURNAL OF LIPID RESEARCH
(2022)