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  • Journal article

  • Authors : Schäfer, an-Hannes (2023)

  • Sphingolipids are structural membrane components that also function in cellular stress 32 responses. The serine palmitoyl-transferase (SPT) catalyzes the rate limiting step in 33 sphingolipid biogenesis. Its activity is tightly regulated through multiple binding part-34 ners, including Tsc3, Orm proteins, ceramides, and the phosphatidylinositol-4-phos-35 phate (PI4P) phosphatase Sac1. The structural organization and regulatory mecha-36 nisms of this complex are not yet understood.

  • Journal Article

  • Authors : Williamson, Lainey J.  (2023)

  • Tpp49Aa1 from Lysinibacillus sphaericus is a Toxin_10 family protein that – in combination with Cry48Aa1, a 3-domain crystal protein - has potent mosquitocidal activity, specifically against Culex quinquefasciatus mosquitoes. MHz serial femtosecond crystallography at a nano-focused X-ray free electron laser, allowed rapid and high-quality data collection to determine the Tpp49Aa1 structure at 1.62 Å resolution from native nanocrystals. This revealed the packin...

  • Journal article

  • Authors : Anderson, Thomas K. (2023)

  • Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from the betacoronaviruses like SARS-CoV and SARSCoV- 2, the latter of which is the causative agent of COVID-19. In...

  • Journal article

  • Authors : Watson, James A. (2023)

  • Spalt-like 4 (SALL4) maintains vertebrate embryonic stem cell identity and is required for the development of multiple organs, including limbs. Mutations in SALL4 are associated with Okihiro syndrome and SALL4 is also a known target of thalidomide. SALL4 protein has a distinct preference for AT-rich sequences, recognised by a pair of zinc fingers at the C-terminus. However, unlike many characterised zinc finger proteins, SALL4 shows flexibl...

  • Journal article

  • Authors : Rutledge, Hannah L. (2023)

  • The enzyme nitrogenase couples adenosine triphosphate (ATP) hydrolysis to the multi-electron reduction of atmospheric dinitrogen into ammonia. Despite extensive research, the mechanistic details of ATP-dependent energy transduction and dinitrogen reduction by nitrogenase are not well understood, requiring new strategies to monitor its structural dynamics during catalytic action. Here we report the cryogenic electron microscopic interrogation of the nitrogenase complex under enzymatic ...

  • Journal article

  • Authors : Banerjee, Sayanika (2023)

  • Ufmylation, a protein modification by Ubiquitin-like (UBL) protein UFM1, plays a crucial role in several cellular processes including DNA damage response, protein translation and ER homeostasis. To date, little is known how the enzymes responsible for this modification coordinate their action. Here we have studied the details of UFL1 (E3) activity, its binding to UFC1 (E2), and its relation to UBA5 (E1), using a combination of structur...

  • Journal article

  • Authors : Shafiei, Alaleh (2023)

  • Frataxin is a 23 KDa mitochondrial iron-binding protein that is involved in biogenesis of iron sulfur clusters. A deficiency in frataxin leads to Friedreich's ataxia, a progressive neurodegenerative disorder. The bacterial ortholog of eukaryotic mitochondrial frataxin, CyaY, is thought to play a role in iron sulfur cluster assembly as an iron supplier, making it an important target for study. Here, we present the first ambient tem...

  • Journal article

  • Authors : Onishi, Shuhei  (2023)

  • Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To reveal the structural basis of H2BK120 ubiquitination and its regulation, we determined the cryo-EM structure of...

  • Journal article

  • Authors : Richards, Logan S. (2023)

  • Amyloid diseases are linked to the formation and persistence of large, multimeric structures in various tissues. Amyloid fibrils are characterized by a cross-beta scaffold in which identical protein molecules mate tightly as beta-strands to form a long, unbranched fibril1,2. Before amyloid-forming proteins assemble into fibrils, they can display a globular fold, requiring partial or total unfolding to convert into an amyloid state3,4. Debilitating ne...