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Showing 1–18 of 18 results
Advanced filters: Author: Rajat Rohatgi Clear advanced filters

  • The structural mechanism of a natively isolated GRP94 folding intermediate tethered to a CCDC134-bound translocon is described, revealing how the nascent chain remodels the translocon to control N-glycosylation by OST.

    • Melvin Yamsek
    • Mengxiao Ma
    • Robert J. Keenan
    ResearchOpen Access
    Nature
    Volume: 649, P: 777-784

  • The Hedgehog (Hh) pathway plays central roles in animal development and stem-cell function. Defects in Hh signalling lead to birth defects and cancer in humans. The first and often genetically damaged step in this pathway is the interaction between two membrane proteins — Patched (Ptc), encoded by a tumour suppressor gene, and Smoothened (Smo), encoded by a proto-oncogene. Recent work linking Hh signalling to sterol metabolites and protein-trafficking events at the primary cilium promises to shed light on the biochemical basis of how Patched inhibits Smoothened, and to provide new avenues for cancer treatment.

    • Rajat Rohatgi
    • Matthew P. Scott
    Reviews
    Nature Cell Biology
    Volume: 9, P: 1005-1009

  • 20(S)-hydroxycholesterol binds to Smo at a site distinct from cyclopamine and activates signaling via an allosteric mechanism. A new alkyne oxysterol analog selectively captures Smo from membrane extracts and provides a new method for detecting protein-sterol interactions.

    • Sigrid Nachtergaele
    • Laurel K Mydock
    • Rajat Rohatgi
    Research
    Nature Chemical Biology
    Volume: 8, P: 211-220

  • Wnt receptors are controlled by their ubiquitin-mediated proteolysis. The authors show that the USP46 deubiquitylase complex potentiates Wnt signaling in human cells, Xenopus, and zebrafish by inhibiting cell surface LRP6 degradation.

    • Victoria H. Ng
    • Zachary Spencer
    • Ethan Lee
    ResearchOpen Access
    Nature Communications
    Volume: 14, P: 1-13

  • Hedgehog-Interacting Protein (HHIP) is the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling. Here, the authors report structures of the HHIP N- and C-terminal domains, both in complexes with glycosaminoglycans, providing insights into the molecular basis for SHH sequestration and inhibition.

    • Samuel C. Griffiths
    • Rebekka A. Schwab
    • Christian Siebold
    ResearchOpen Access
    Nature Communications
    Volume: 12, P: 1-13

  • TDP43 regulates RNA processing and undergoes liquid-liquid phase separation. Here, the authors combine bioinformatic analysis and quantitative measurements of phase properties in living cells to uncover the rules that link the amino acid sequence of TDP43 with its phase properties and find that unexpectedly, mutants of TDP43 that are deficient in phase separation can still function to mediate splicing.

    • Hermann Broder Schmidt
    • Ariana Barreau
    • Rajat Rohatgi
    ResearchOpen Access
    Nature Communications
    Volume: 10, P: 1-14

  • Tubulin post-translational modifications (PTMs) occur spatiotemporally throughout cells, therefore assessing the physiological roles in specific subcellular compartments has been challenging. Here the authors develop a method to rapidly deplete tubulin glutamylation inside the primary cilia by targeting an engineered deglutamylase to the axoneme.

    • Shi-Rong Hong
    • Cuei-Ling Wang
    • Yu-Chun Lin
    ResearchOpen Access
    Nature Communications
    Volume: 9, P: 1-13

  • Cholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular domain

    • Amalie F. Rudolf
    • Maia Kinnebrew
    • Christian Siebold
    Research
    Nature Chemical Biology
    Volume: 15, P: 975-982

  • Lasonolide A is hydrolyzed into a cytotoxic metabolite by a lipid droplet-associated orphan serine hydrolase, showing that lipid droplets can promote drug toxicity by both accumulating and metabolizing drugs in cells.

    • Ramin Dubey
    • Craig E. Stivala
    • Rajat Rohatgi
    Research
    Nature Chemical Biology
    Volume: 16, P: 206-213

  • Structural studies show that the activity of the G-protein-coupled receptor Smoothened is modulated by ligand-regulated interactions between its extracellular and transmembrane domains.

    • Eamon F. X. Byrne
    • Ria Sircar
    • Christian Siebold
    Research
    Nature
    Volume: 535, P: 517-522

  • Chemically inducible diffusion trap at cilia (CIDTc), a method to trap proteins in the cilia, was applied to study the kinetics of protein accumulation and reveal a molecular sieve at the ciliary base. CIDTc can also be applied to study signaling pathways in the cilia.

    • Yu-Chun Lin
    • Pawel Niewiadomski
    • Takanari Inoue
    Research
    Nature Chemical Biology
    Volume: 9, P: 437-443

  • The Hedgehog (Hh) receptor PTCH1 uses its transporter-like function to inhibit the GPCR SMO by limiting the pool of accessible membrane cholesterol. Cholesterol acts as a ligand for SMO to activate downstream signaling.

    • Arun Radhakrishnan
    • Rajat Rohatgi
    • Christian Siebold
    Reviews
    Nature Chemical Biology
    Volume: 16, P: 1303-1313