Journal: Nature Structural & Molecular Biology

Abbreviation

Struct. Mol. Biol.

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Nature

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ISSN

1545-9993
1545-9985

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Publications1 - 10 of 67
  • Phase separation properties of RPA combine high-affinity ssDNA binding with dynamic condensate functions at telomeres
    Item type: Journal Article
    Spegg, Vincent; Panagopoulos, Andreas; Stout, Merula; et al. (2023)
    Nature Structural & Molecular Biology
    RPA has been shown to protect single-stranded DNA (ssDNA) intermediates from instability and breakage. RPA binds ssDNA with sub-nanomolar affinity, yet dynamic turnover is required for downstream ssDNA transactions. How ultrahigh-affinity binding and dynamic turnover are achieved simultaneously is not well understood. Here we reveal that RPA has a strong propensity to assemble into dynamic condensates. In solution, purified RPA phase separates into liquid droplets with fusion and surface wetting behavior. Phase separation is stimulated by sub-stoichiometric amounts of ssDNA, but not RNA or double-stranded DNA, and ssDNA gets selectively enriched in RPA condensates. We find the RPA2 subunit required for condensation and multi-site phosphorylation of the RPA2 N-terminal intrinsically disordered region to regulate RPA self-interaction. Functionally, quantitative proximity proteomics links RPA condensation to telomere clustering and integrity in cancer cells. Collectively, our results suggest that RPA-coated ssDNA is contained in dynamic RPA condensates whose properties are important for genome organization and stability.
  • The Hsp70 Ssz1 modulates the function of the ribosome-associated J-protein Zuo1
    Item type: Journal Article
    Huang, Peggy; Gautschi, Matthias; Walter, William; et al. (2005)
    Nature Structural & Molecular Biology
  • The molecular mechanism of cotranslational membrane protein recognition and targeting by SecA
    Item type: Journal Article
    Wang, Shuai; Jomaa, Ahmad; Jaskolowski, Mateusz; et al. (2019)
    Nature Structural & Molecular Biology
    Cotranslational protein targeting is a conserved process for membrane protein biogenesis. In Escherichia coli, the essential ATPase SecA was found to cotranslationally target a subset of nascent membrane proteins to the SecYEG translocase at the plasma membrane. The molecular mechanism of this pathway remains unclear. Here we use biochemical and cryoelectron microscopy analyses to show that the amino-terminal amphipathic helix of SecA and the ribosomal protein uL23 form a composite binding site for the transmembrane domain (TMD) on the nascent protein. This binding mode further enables recognition of charged residues flanking the nascent TMD and thus explains the specificity of SecA recognition. Finally, we show that membrane-embedded SecYEG promotes handover of the translating ribosome from SecA to the translocase via a concerted mechanism. Our work provides a molecular description of the SecA-mediated cotranslational targeting pathway and demonstrates an unprecedented role of the ribosome in shielding nascent TMDs.
  • Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes
    Item type: Journal Article
    Striebel, Frank; Imkamp, Frank; Sutter, Markus; et al. (2009)
    Nature Structural & Molecular Biology
  • Thomas Steitz 1940-2018
    Item type: Other Journal Item
    Ban, Nenad (2018)
    Nature Structural & Molecular Biology
  • Global, in situ analysis of the structural proteome in individuals with Parkinson's disease to identify a new class of biomarker
    Item type: Journal Article
    Mackmull, Marie-Therese; Nagel, Luise; Sesterhenn, Fabian; et al. (2022)
    Nature Structural & Molecular Biology
    Parkinson's disease (PD) is a prevalent neurodegenerative disease for which robust biomarkers are needed. Because protein structure reflects function, we tested whether global, in situ analysis of protein structural changes provides insight into PD pathophysiology and could inform a new concept of structural disease biomarkers. Using limited proteolysis-mass spectrometry (LiP-MS), we identified 76 structurally altered proteins in cerebrospinal fluid (CSF) of individuals with PD relative to healthy donors. These proteins were enriched in processes misregulated in PD, and some proteins also showed structural changes in PD brain samples. CSF protein structural information outperformed abundance information in discriminating between healthy participants and those with PD and improved the discriminatory performance of CSF measures of the hallmark PD protein alpha-synuclein. We also present the first analysis of inter-individual variability of a structural proteome in healthy individuals, identifying biophysical features of variable protein regions. Although independent validation is needed, our data suggest that global analyses of the human structural proteome will guide the development of novel structural biomarkers of disease and enable hypothesis generation about underlying disease processes.
  • Probing Gα i1 protein activation at single-amino acid resolution
    Item type: Journal Article
    Sun, Dawei; Flock, Tilman; Deupi, Xavier; et al. (2015)
    Nature Structural & Molecular Biology
    We present comprehensive maps at single–amino acid resolution of the residues stabilizing the human Gαi1 subunit in nucleotide- and receptor-bound states. We generated these maps by measuring the effects of alanine mutations on the stability of Gαi1 and the rhodopsin–Gαi1 complex. We identified stabilization clusters in the GTPase and helical domains responsible for structural integrity and the conformational changes associated with activation. In activation cluster I, helices α1 and α5 pack against strands β1–β3 to stabilize the nucleotide-bound states. In the receptor-bound state, these interactions are replaced by interactions between α5 and strands β4–β6. Key residues in this cluster are Y320, which is crucial for the stabilization of the receptor-bound state, and F336, which stabilizes nucleotide-bound states. Destabilization of helix α1, caused by rearrangement of this activation cluster, leads to the weakening of the interdomain interface and release of GDP.
  • Shape-specific recognition in the structure of the Vts1p SAM domain with RNA
    Item type: Journal Article
    Oberstrass, Florian C.; Lee, Albert; Stefl, Richard; et al. (2006)
    Nature Structural & Molecular Biology
  • Mechanistic diversity in ATP-binding cassette (ABC) transporters
    Item type: Review Article
    Locher, Kaspar P. (2016)
    Nature Structural & Molecular Biology
  • Structural basis of small-molecule inhibition of human multidrug transporter ABCG2
    Item type: Journal Article
    Jackson, Scott M.; Manolaridis, Ioannis; Kowal, Julia; et al. (2018)
    Nature Structural & Molecular Biology
Publications1 - 10 of 67