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  • Journal article

  • The Architecture of GluD2 Ionotropic Delta Glutamate Receptor Elucidated by cryo-EM

    • Authors : Burada, Ananth Prasad; Kumar, Janesh (2020)

  • GluD2 receptors belong to the orphan delta receptor family of glutamate receptor ion channels. These receptors play key roles in synaptogenesis and synaptic plasticity and are associated with multiple neuronal disorders like schizophrenia, autism spectrum disorder, cerebellar ataxia, intellectual disability, paraplegia, retinal dystrophy, etc. Despite the importance of these receptors in CNS, insights into full-length GluD2 receptor structure is missing till-date. Here we r...
  • Journal article

  • A binary arginine methylation switch on histone H3 Arginine 2 regulates its interaction with WDR5

    • Authors : Lorton, Benjamin M; Harijan, Rajesh K; Burgos, Emmanuel S (2020)

  • Using highly accurate quantitative binding analysis combined with high-resolution crystal structures of WDR5 in complex with unmodified (me0) and me1/me2s L-Arginine amino acids and in complex with H3R2me1 peptide, we provide a rigorous biochemical study of this important biological interaction. Despite modest structural differences at the binding interface, our study supports an interaction model regulated by a binary arginine methylation switch: H3R2me2a prevents int...
  • Journal article

  • Functionalized Mesoporous Silicas Direct Structural Polymorphism of Amyloid-β Fibrils

    • Authors : Lucas, Michael J; Pan, Henry S; Verbeke, Eric J (2020)

  • A major challenge in understanding the progression of Alzheimer’s Disease lies in the various fibril structures, or polymorphs, adopted by Amyloid-β (Aβ). Heterogenous fibril populations may be responsible for different disease phenotypes and growing evidence suggests that Aβ fibrils formed in vitro are structurally distinct from patient-derived fibrils. To help bridge this gap, we used surface-functionalized mesoporous silicas to influence the formation of Aβ1-40 fibr...
  • Journal article

  • The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

    • Authors : Lucas, Michael J; Pan, Henry S; Verbeke, Eric J (2020)

  • A common variant in the manganese transporter SLC39A8 is associated with numerous phenotypes including schizophrenia. Mealer et. al. presents an in-depth analysis of brain MRI and plasma glycomics in human carriers of the common variant, identifying several manganese-related changes with potential for diagnostic and therapeutic biomarker development.
  • Journal article

  • Dissecting the nanoscale lipid profile of caveolae

    • Authors : Zhou, Yong; Ariotti, Nicholas; Rae, James (2020)

  • Caveolae are specialized domains of the vertebrate cell surface with a well-defined morphology and crucial roles in cell migration and mechanoprotection. Unique compositions of proteins and lipids determine membrane architectures. The precise caveolar lipid profile and the roles of the major caveolar structural proteins, caveolins and cavins, in selectively sorting lipids have not been defined. Here we used quantitative nanoscale lipid mapping together with molecular&#...
  • Journal article

  • Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein

    • Authors : Harrington, Haley R; Zimmer, Matthew H; Chamness, Laura M (2020)

  • Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work we show that the forces generated by the cotranslational folding of the nascent polypeptide...
  • Journal article

  • Characterization of Prenylated C-terminal Peptides Using a Novel Capture Technique Coupled with LCMS

    • Authors : Wilkins, James A; Kaasik, Krista; Chalkley, Robert J (2020)

  • Post-translational modifications play a critical and diverse role in regulating cellular activities. Despite their fundamentally important role in cellular function, there has been no report to date of an effective generalized approach to the targeting, extraction and characterization of the critical c-terminal regions of natively prenylated proteins. Various chemical modification and metabolic labelling strategies in cell culture have been reported. However, their applicability...
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  • Solid-Phase Peptide Capture and Release for Bulk and Single-Molecule Proteomics

    • Authors : Howard, Cecil J; Floyd, Brendan M; Bardo, Angela M (2020)

  • The field of proteomics has expanded recently with more sensitive techniques for the bulk measurement of peptides as well as single-molecule techniques. One limiting factor for some of these methods is the need for multiple chemical derivatizations and highly pure proteins free of contaminants. We demonstrate a solid-phase capture strategy suitable for the proteolysis, purification, and subsequent chemical modification of peptides. We use this resin on an...