Npj structural biology最新文献

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Structural basis for Mg²⁺-glycine synergy in the tandem glycine riboswitch revealed by cryo-EM. cryo-EM揭示了Mg 2 + -甘氨酸在串联甘氨酸核糖开关中协同作用的结构基础。

Npj structural biology Pub Date : 2026-01-01 Epub Date: 2026-10-01 DOI: 10.1038/s44511-026-00002-y

Nathan Jespersen, Jigneshkumar Dahyabhai Prajapati, Ankush Singhal, Karissa Y Sanbonmatsu

{"title":"Structural basis for Mg²⁺-glycine synergy in the tandem glycine riboswitch revealed by cryo-EM.","authors":"Nathan Jespersen, Jigneshkumar Dahyabhai Prajapati, Ankush Singhal, Karissa Y Sanbonmatsu","doi":"10.1038/s44511-026-00002-y","DOIUrl":"10.1038/s44511-026-00002-y","url":null,"abstract":"Riboswitches are non-coding RNA sequences that control cellular processes through ligand binding. Conformational heterogeneity is fundamental to riboswitch functionality, yet this same attribute makes structural characterization of these mRNA elements challenging. Here, we use cryo-electron microscopy to characterize different structural populations of the glycine riboswitch tandem aptamers, and molecular dynamics simulations to support the observed ligand orientation in the holo state. We find that Mg2+ enables formation of the fully folded \"walking man\" conformation, which consists of a rigidified core and two dynamic helices, but is insufficient on its own to make this the dominant state. In Mg²⁺ conditions alone, approximately one-third of the picked particles are fully folded, whereas two thirds adopt distinct, partially folded states. Glycine interactions further stabilize the fully folded conformation, doubling the relative population of fully folded particles by stabilizing a conserved inter-aptamer Hoogsteen base pair, enabling our capture of a 2.9 Å-resolution structure for this RNA-only system. The population data show that glycine and Mg²⁺ operate synergistically: glycine enhances Mg²⁺ localization, while Mg2+ drives glycine recruitment. Our findings indicate that cryo-electron microscopy offers a promising avenue to characterize RNA folding ensembles.","PeriodicalId":524242,"journal":{"name":"Npj structural biology","volume":"1 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of activation of an ancestral TEC kinase by PIP₃. PIP3激活祖先TEC激酶的机制。

Npj structural biology Pub Date : 2026-01-01 Epub Date: 2026-10-01 DOI: 10.1038/s44511-026-00001-z

Eva Krötenheerdt, Lucas Piëch, Freia von Raußendorf, Ronja Reinhardt, Ranjana Nataraj, Nicholas Wedige, Hunter G Nyvall, Emma E Walsh, John E Burke, Thomas A Leonard

{"title":"Mechanism of activation of an ancestral TEC kinase by PIP3.","authors":"Eva Krötenheerdt, Lucas Piëch, Freia von Raußendorf, Ronja Reinhardt, Ranjana Nataraj, Nicholas Wedige, Hunter G Nyvall, Emma E Walsh, John E Burke, Thomas A Leonard","doi":"10.1038/s44511-026-00001-z","DOIUrl":"10.1038/s44511-026-00001-z","url":null,"abstract":"The TEC kinases are a family of five paralogous mammalian genes that play crucial roles in cell growth, proliferation, and differentiation, particularly in immune cells. The recruitment and activation of the TEC kinases depend on the generation of the lipid second messenger, PIP3, in the plasma membrane. However, the mechanisms by which PIP3 activates the TEC kinases are not well understood. By studying an ancestral TEC kinase from the choanoflagellate Monosiga brevicollis, we have elucidated an evolutionarily conserved mechanism for the activation of the TEC kinases by PIP3. We demonstrate that PIP3, but not PIP2, relieves autoinhibition by displacing the PH domain of MbTEC from a conserved intramolecular interaction with its kinase domain. We also show that a conserved polyproline motif within MbTEC promotes its activation in a kinase-intrinsic mechanism. Finally, we show that the PH domain is sufficient to restore autoinhibition in a constitutively active mutant of MbTEC. Our findings reveal that PIP3 is necessary but not sufficient for MbTEC activation.","PeriodicalId":524242,"journal":{"name":"Npj structural biology","volume":"1 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0