Biochemical Society transactions最新文献_第9页

The high-affinity tryptophan uptake transport system in human cells. 人体细胞中的高亲和性色氨酸吸收转运系统。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20230742

Keisuke Wakasugi, Takumi Yokosawa

引用次数: 0

Lessons from natural molecular glue degraders. 天然分子胶降解剂的启示

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20230836

Shiyun Cao

{"title":"Lessons from natural molecular glue degraders.","authors":"Shiyun Cao","doi":"10.1042/BST20230836","DOIUrl":"10.1042/BST20230836","url":null,"abstract":"Molecular glue (MG) degraders include plant hormones and therapeutic drugs and have become a hot topic in drug discovery. Unlike bivalent proteolysis targeting chimeras (PROTACs), monovalent MGs can trigger the degradation of non-ligandable proteins by enhancing their interaction with E3 ubiquitin ligases. Here, I analyze the characteristics of natural MG degraders, contrast them with synthetic ones, and provide a rationale for optimizing MGs. In natural MG-based degradation systems, a stable complex is only formed when all three partners (MG, E3 ligase, and substrate) are present, while the affinities between any two components are either weak or undetectable. After the substrate is degraded, the MG will dissociate from its receptor (E3 ligase) due to their low micromolar affinity. In contrast, synthetic MGs, such as immunomodulatory drugs (IMiDs) and CR8, are potent inhibitors of their receptors by blocking the CRBN-native substrate interaction or by occupying the active site of CDK12. Inspired by nature, the affinities of IMiDs to CRBN can be reduced to make those compounds degraders without the E3-inhibitory activity, therefore, minimizing the interference with the physiological substrates of CRBN. Similarly, the CR8-CDK interaction can be weakened to uncouple the degrader function from the kinase inhibition. To mimic natural examples and reduce side effects, future development of MG degraders that lack the inhibitory activity should be considered.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA. 先天性免疫受体 RIG-I 的校对机制：区分自身和病毒 RNA。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20230724

Mihai Solotchi, Smita S Patel

{"title":"Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.","authors":"Mihai Solotchi, Smita S Patel","doi":"10.1042/BST20230724","DOIUrl":"10.1042/BST20230724","url":null,"abstract":"The RIG-I-like receptors (RLRs), comprising retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), are pattern recognition receptors belonging to the DExD/H-box RNA helicase family of proteins. RLRs detect viral RNAs in the cytoplasm and respond by initiating a robust antiviral response that up-regulates interferon and cytokine production. RIG-I and MDA5 complement each other by recognizing different RNA features, and LGP2 regulates their activation. RIG-I's multilayered RNA recognition and proofreading mechanisms ensure accurate viral RNA detection while averting harmful responses to host RNAs. RIG-I's C-terminal domain targets 5'-triphosphate double-stranded RNA (dsRNA) blunt ends, while an intrinsic gating mechanism prevents the helicase domains from non-specifically engaging with host RNAs. The ATPase and RNA translocation activity of RIG-I adds another layer of selectivity by minimizing the lifetime of RIG-I on non-specific RNAs, preventing off-target activation. The versatility of RIG-I's ATPase function also amplifies downstream signaling by enhancing the signaling domain (CARDs) exposure on 5'-triphosphate dsRNA and promoting oligomerization. In this review, we offer an in-depth understanding of the mechanisms RIG-I uses to facilitate viral RNA sensing and regulate downstream activation of the immune system.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330305","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

Research progress of ZIC5 for tumor metastasis. ZIC5治疗肿瘤转移的研究进展。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20231263

Yiming Zhong, Shangzhi Yang, Xianli Wang, Chuanyu Sun

引用次数: 0

Nano-organization of synaptic calcium signaling. 突触钙信号的纳米组织

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20231385

Clara I McCarthy, Ege T Kavalali

{"title":"Nano-organization of synaptic calcium signaling.","authors":"Clara I McCarthy, Ege T Kavalali","doi":"10.1042/BST20231385","DOIUrl":"10.1042/BST20231385","url":null,"abstract":"Recent studies suggest an exquisite structural nano-organization within single synapses, where sites of evoked fusion - marked by clustering of synaptic vesicles, active zone proteins and voltage-gated calcium channels - are directly juxtaposed to postsynaptic receptor clusters within nanocolumns. This direct nanometer scale alignment between presynaptic fusion apparatus and postsynaptic receptors is thought to ensure the fidelity of synaptic signaling and possibly allow multiple distinct signals to occur without interference from each other within a single active zone. The functional specificity of this organization is made possible by the inherent nano-organization of calcium signals, where all the different calcium sources such as voltage-gated calcium channels, intracellular stores and store-operated calcium entry have dedicated local targets within their nanodomain to ensure precision of action. Here, we discuss synaptic nano-organization from the perspective of calcium signals, where some of the principal findings from early work in the 1980s continue to inspire current studies that exploit new genetic tools and super-resolution imaging technologies.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943798","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

Exploring the role non-coding RNAs during myocardial cell fate. 探索非编码 RNA 在心肌细胞命运中的作用

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20231216

Diego Franco, Cristina Sánchez-Fernández, Carlos García-Padilla, Estefania Lozano-Velasco

引用次数: 0

Mechanoimmunology in the solid tumor microenvironment. 实体肿瘤微环境中的机制免疫学。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20231427

Matteo Golo, Peter L H Newman, Daryan Kempe, Maté Biro

{"title":"Mechanoimmunology in the solid tumor microenvironment.","authors":"Matteo Golo, Peter L H Newman, Daryan Kempe, Maté Biro","doi":"10.1042/BST20231427","DOIUrl":"10.1042/BST20231427","url":null,"abstract":"The tumor microenvironment (TME) is a complex and dynamic ecosystem that adjoins the cancer cells within solid tumors and comprises distinct components such as extracellular matrix, stromal and immune cells, blood vessels, and an abundance of signaling molecules. In recent years, the mechanical properties of the TME have emerged as critical determinants of tumor progression and therapeutic response. Aberrant mechanical cues, including altered tissue architecture and stiffness, contribute to tumor progression, metastasis, and resistance to treatment. Moreover, burgeoning immunotherapies hold great promise for harnessing the immune system to target and eliminate solid malignancies; however, their success is hindered by the hostile mechanical landscape of the TME, which can impede immune cell infiltration, function, and persistence. Consequently, understanding TME mechanoimmunology - the interplay between mechanical forces and immune cell behavior - is essential for developing effective solid cancer therapies. Here, we review the role of TME mechanics in tumor immunology, focusing on recent therapeutic interventions aimed at modulating the mechanical properties of the TME to potentiate T cell immunotherapies, and innovative assays tailored to evaluate their clinical efficacy.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PROPPINs and membrane fission in the endo-lysosomal system. 内溶酶体系统中的 PROPPINs 和膜裂变。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20230897

Navin Gopaldass, Andreas Mayer

引用次数: 0

Let's get fat: emergence of S-acylation as a therapeutic target in Huntington disease. 让我们胖起来：S-酰化成为亨廷顿病的治疗靶点。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20231290

Dale D O Martin, Shaun S Sanders

引用次数: 0

Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission. 超乎年龄的成熟：尽管生活在疟疾高度传播的环境中，但仍有幼儿未能被检测出寄生虫血症。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-06-26 DOI: 10.1042/BST20230401

Prasida Holla, Jyoti Bhardwaj, Tuan M Tran

{"title":"Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission.","authors":"Prasida Holla, Jyoti Bhardwaj, Tuan M Tran","doi":"10.1042/BST20230401","DOIUrl":"10.1042/BST20230401","url":null,"abstract":"Despite having the highest risk of progressing to severe disease due to lack of acquired immunity, the youngest children living in areas of highly intense malaria transmission have long been observed to be infected at lower rates than older children. Whether this observation is due to reduced exposure to infectious mosquito bites from behavioral and biological factors, maternally transferred immunity, genetic factors, or enhanced innate immunity in the young child has intrigued malaria researchers for over half a century. Recent evidence suggests that maternally transferred immunity may be limited to early infancy and that the young child's own immune system may contribute to control of malarial symptoms early in life and prior to the development of more effective adaptive immunity. Prospective studies of active and passive detection of Plasmodium falciparum blood-stage infections have identified young children (<5 years old) who remain uninfected through a defined surveillance period despite living in settings of highly intense malaria transmission. Yet, little is known about the potential immunological basis for this 'aparasitemic' phenotype. In this review, we summarize the observational evidence for this phenotype in field studies and examine potential reasons why these children escape detection of parasitemia, covering factors that are either extrinsic or intrinsic to their developing immune system. We discuss the challenges of distinguishing malaria protection from lack of malaria exposure in field studies. We also identify gaps in our knowledge regarding cellular immunity in the youngest age group and propose directions that researchers may take to address these gaps.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943795","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