Versees W.,Vrije Universiteit Brussel |
Versees W.,Structural biology research center
Structure | Year: 2015
In this issue of Structure, Glatt and colleagues report the structure of the Kti11/Kti13 heterodimer. This study reveals how dimerization and Fe2+ binding are required for modification of both tRNA and EF2, thus suggesting a mechanism for regulation of translation elongation via two different pathways. © 2015 Elsevier Ltd. Source
De Meyer T.,Vlaams Institute for Biotechnology |
De Meyer T.,Ghent University |
Muyldermans S.,Structural biology research center |
Muyldermans S.,Vrije Universiteit Brussel |
And 2 more authors.
Trends in Biotechnology | Year: 2014
Since the serendipitous discovery 20 years ago of bona fide camelid heavy-chain antibodies, their single-domain antigen-binding fragments, known as VHHs or nanobodies, have received a progressively growing interest. As a result of the beneficial properties of these stable recombinant entities, they are currently highly valued proteins for multiple applications, including fundamental research, diagnostics, and therapeutics. Today, with the original patents expiring, even more academic and industrial groups are expected to explore innovative VHH applications. Here, we provide a thorough overview of novel implementations of VHHs as research and diagnostic tools, and of the recently evaluated production platforms for several VHHs and VHH-derived antibody formats. © 2014 Elsevier Ltd. Source
Efremov R.G.,Max Planck Institute of Molecular Physiology |
Efremov R.G.,Structural biology research center |
Efremov R.G.,Vrije Universiteit Brussel |
Leitner A.,ETH Zurich |
And 3 more authors.
Nature | Year: 2015
Muscle contraction is initiated by the release of calcium (Ca2+) from the sarcoplasmic reticulum into the cytoplasm of myocytes through ryanodine receptors (RyRs). RyRs are homotetrameric channels with a molecular mass of more than 2.2 megadaltons that are regulated by several factors, including ions, small molecules and proteins. Numerous mutations in RyRs have been associated with human diseases. The molecular mechanism underlying the complex regulation of RyRs is poorly understood. Using electron cryomicroscopy, here we determine the architecture of rabbit RyR1 at a resolutionof 6.1A° .We showthat the cytoplasmicmoiety ofRyR1containstwo largea-solenoiddomainsandseveralsmaller domains, with folds suggestive of participation in protein-protein interactions. The transmembrane domain represents a chimaera of voltage-gated sodiumand pH-activated ion channels.Weidentify the calcium-binding EF-hand domain and show that it functions as a conformational switch allosterically gating the channel. © 2015 Macmillan Publishers Limited. Source
Huang W.,Stanford University |
Manglik A.,Stanford University |
Venkatakrishnan A.J.,Stanford University |
Laeremans T.,Vrije Universiteit Brussel |
And 16 more authors.
Nature | Year: 2015
Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective analgesics. To shed light on the structural basis for μOR activation, here we report a 2.1 Å X-ray crystal structure of the murine μOR bound to the morphinan agonist BU72 and a G protein mimetic camelid antibody fragment. The BU72-stabilized changes in the μOR binding pocket are subtle and differ from those observed for agonist-bound structures of the β 2 -adrenergic receptor (β 2 AR) and the M2 muscarinic receptor. Comparison with active β 2 AR reveals a common rearrangement in the packing of three conserved amino acids in the core of the μOR, and molecular dynamics simulations illustrate how the ligand-binding pocket is conformationally linked to this conserved triad. Additionally, an extensive polar network between the ligand-binding pocket and the cytoplasmic domains appears to play a similar role in signal propagation for all three G-protein-coupled receptors. © 2015 Macmillan Publishers Limited. All rights reserved. Source
Hubin E.,University of Twente |
Hubin E.,Vrije Universiteit Brussel |
Hubin E.,Structural biology research center |
Van Nuland N.A.J.,Vrije Universiteit Brussel |
And 3 more authors.
Cellular and Molecular Life Sciences | Year: 2014
The aggregation and deposition of the amyloid-β peptide (Aβ) in the brain has been linked with neuronal death, which progresses in the diagnostic and pathological signs of Alzheimer's disease (AD). The transition of an unstructured monomeric peptide into self-assembled and more structured aggregates is the crucial conversion from what appears to be a harmless polypeptide into a malignant form that causes synaptotoxicity and neuronal cell death. Despite efforts to identify the toxic form of Aβ, the development of effective treatments for AD is still limited by the highly transient and dynamic nature of interconverting forms of Aβ. The variability within the in vivo "pool" of different Aβ peptides is another complicating factor. Here we review the dynamical interplay between various components that influence the heterogeneous Aβ system, from intramolecular Aβ flexibility to intermolecular dynamics between various Aβ alloforms and external factors. The complex dynamics of Aβ contributes to the causative role of Aβ in the pathogenesis of AD. © 2014 The Author(s). Source