Molecules and Cells最新文献_第2页

Cryo-EM structures of mouse bestrophin 1 channel in closed and partially open conformations 小鼠strophin - 1通道封闭和部分开放构象的低温电镜结构。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-03-03 DOI: 10.1016/j.mocell.2025.100208

Kwon-Woo Kim , Euna Lee , Ara Ko , Junmo Hwang , Kunwoong Park , Byoung-Cheol Lee , Ki Woo Kim , Won-Jong Oh , Kyuhyung Kim , Hyun-Ho Lim

{"title":"Cryo-EM structures of mouse bestrophin 1 channel in closed and partially open conformations","authors":"Kwon-Woo Kim , Euna Lee , Ara Ko , Junmo Hwang , Kunwoong Park , Byoung-Cheol Lee , Ki Woo Kim , Won-Jong Oh , Kyuhyung Kim , Hyun-Ho Lim","doi":"10.1016/j.mocell.2025.100208","DOIUrl":"10.1016/j.mocell.2025.100208","url":null,"abstract":"<div><div>Bestrophin 1 (BEST1) channels are calcium-activated Cl<sup>−</sup> channels involved in diverse physiological processes, including gliotransmitter release in astrocytes. Although human and chicken BEST1 orthologs have been extensively studied, the structural and functional properties of mouse BEST1 (mBEST1) remain poorly understood. In this study, we characterized the structure-function of mBEST1-BF, a C–terminally tagged variant, using whole-cell patch-clamp recordings, surface biotinylation assays, and single-particle cryo-electron microscopy. Cryo-electron microscopy structural analysis of mBEST1-BF revealed closed and partially open conformations. Comparative analysis with human and chicken BEST1 orthologs highlighted conserved calcium-binding and gating mechanisms, with distinct features in mBEST1, including a wider aperture sufficient to accommodate dehydrated Cl<sup>−</sup> ions and potential anion-binding sites near Val205 and Gln208 residues. The disordered C-terminal region of mBEST1 remains unresolved, suggesting it may require stabilizing factors for structural determination. Additionally, the autoinhibitory domain, which includes Ser354, likely plays a key role in regulating gating, with Ser354 potentially serving as a phosphorylation site that modulates channel activity. Our findings provide structural and functional insights into mBEST1 and suggest mechanisms underlying its unique gating and ion permeation properties.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 5","pages":"Article 100208"},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein-O-fucosylation of coreceptors may be required for Nodal signaling in Xenopus 非洲爪蟾的节点信号可能需要共受体的蛋白o聚焦。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-03-03 DOI: 10.1016/j.mocell.2025.100207

Yeon-Jin Kim , Seung-Joo Nho , Soo Young Lee , Chang-Yeol Yeo

{"title":"Protein-O-fucosylation of coreceptors may be required for Nodal signaling in Xenopus","authors":"Yeon-Jin Kim , Seung-Joo Nho , Soo Young Lee , Chang-Yeol Yeo","doi":"10.1016/j.mocell.2025.100207","DOIUrl":"10.1016/j.mocell.2025.100207","url":null,"abstract":"<div><div>Nodal-related ligands of TGF-β family play pivotal roles for mesoderm induction and body axis formation during vertebrate early embryogenesis. Nodal ligands are distinct from most other TGF-β ligands family as they require EGF-CFC factors as coreceptors for signaling, in addition to their cognate type I and type II TGF-β receptors. In amphibian <em>Xenopus laevis</em> embryos, 5 <em>Nodal-related</em> genes (<em>Xnr1/2/4/5/6</em>) and 2 <em>EGF-CFC</em> genes (<em>XCR1</em>, <em>XCR3</em>) play roles in mesoderm induction and the accumulation of phosphorylated Smad2, while in mammalian embryos, 1 <em>Nodal</em> gene and 1 <em>EGF-CFC</em> gene (<em>Cripto</em>) play roles during mesoderm induction. Mammalian EGF-CFC factors are reported to be <em>O</em>-fucosylated at a conserved threonine residue of the EGF-like motif by protein-<em>O</em>-fucosyltransferase 1 (Pofut1), but this <em>O</em>-fucose modification is shown to be dispensable for Nodal signaling in mammalian embryos. In this study, we investigated the developmental roles of <em>Xenopus laevis Pofut1</em> (<em>XPofut1</em>) and its potential function in Nodal signaling. We found that morpholino antisense-mediated knockdown of <em>XPofut1</em> causes reduction of Smad2 phosphorylation in late blastula and axial truncation in neurula. We also found that the <em>O</em>-fucosyltransferase activity of XPofut1 is important in the marginal zone, but not in the vegetal pole region, of blastula. Interestingly, <em>XPofut1</em> is necessary for Smad2 phosphorylation induced by Xnr1 or Xnr2, but not by Xnr5 or Xnr6. Among the Nodal signaling components, only EGF-CFC factors are known to be modified by Pofut1. Therefore, based on our current observation, we propose that XPofut1 regulates signaling of a subset of nodal ligands in pregastrulation embryos possibly through modulating the function of EGF-CFC factors.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 5","pages":"Article 100207"},"PeriodicalIF":3.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Principles and therapeutics of cancer 癌症的原理和治疗。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-02-28 DOI: 10.1016/j.mocell.2025.100201

Yoontae Lee

引用次数: 0

Omics technologies as powerful approaches to unravel colorectal cancer complexity and improve its management 组学技术是揭示结直肠癌复杂性和改善其管理的有力途径。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-02-28 DOI: 10.1016/j.mocell.2025.100200

Zaynab Fatfat , Marwa Hussein , Maamoun Fatfat , Hala Gali-Muhtasib

{"title":"Omics technologies as powerful approaches to unravel colorectal cancer complexity and improve its management","authors":"Zaynab Fatfat , Marwa Hussein , Maamoun Fatfat , Hala Gali-Muhtasib","doi":"10.1016/j.mocell.2025.100200","DOIUrl":"10.1016/j.mocell.2025.100200","url":null,"abstract":"<div><div>Colorectal cancer (CRC) continues to rank among the deadliest and most prevalent cancers worldwide, necessitating an innovative and comprehensive approach that addresses this serious health challenge at various stages, from screening and diagnosis to treatment and prognosis. As CRC research progresses, the adoption of an omics-centered approach holds transformative potential to revolutionize the management of this disease. Advances in omics technologies encompassing genomics, transcriptomics, proteomics, metabolomics, and epigenomics allow to unravel the oncogenic alterations at these levels, elucidating the intricacies and the heterogeneous nature of CRC. By providing a comprehensive molecular landscape of CRC, omics technologies enable the discovery of potential biomarkers for early non-invasive detection of CRC, definition of CRC subtypes, prediction of its staging, prognosis, and overall survival of CRC patients. They also allow the identification of potential therapeutic targets, prediction of drug response, tracking treatment efficacy, detection of residual disease and cancer relapse, and deciphering the mechanisms of drug resistance. Moreover, they allow the distinction of non-metastatic CRC patients from metastatic ones as well as the stratification of metastatic risk. Importantly, omics technologies open up new opportunities to establish molecular-based criteria to guide the selection of effective treatment paving the way for the personalization of therapy for CRC patients. This review consolidates current knowledge on the omics-based preclinical discoveries in CRC research emphasizing the significant potential of these technologies to improve CRC screening, diagnosis, and prognosis and promote the implementation of personalized medicine to ultimately reduce CRC prevalence and mortality.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 5","pages":"Article 100200"},"PeriodicalIF":3.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover and caption 封面及标题

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-02-26 DOI: 10.1016/S1016-8478(25)00026-3

引用次数: 0

Editorial Board Members/Copyright 编委会成员/版权

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-02-26 DOI: 10.1016/S1016-8478(25)00028-7

引用次数: 0

RIPK3 in necroptosis and cancer RIPK3在坏死下垂和癌症中的作用。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-02-24 DOI: 10.1016/j.mocell.2025.100199