How SARS-CoV-2 binds to human cells
Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. On Friday, March 27 , 2020 Yuanyuan Zhan et al. from Westlake Institute of Advanced Study, Hangzhou, China, published in Science a study entitled Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 where they explain how it binds to human cells...
CIISB offers priority and free-of-charge access for COVID-19 research proposals
CIISB is committed to the use its resources in response to the emergency situation of the COVID-19 virus pandemic. CIISB ensures that available technologies support primarily researchers in their efforts to study the virus and projects aiming to the development of an effective vaccine or treatment.
New EMBO Core Facility Fellowships
EMBO recently launched Core Facility Fellowships, which will support international training exchanges for staff working in core facilities that provide services to research institutes and universities.
Instruct-ERIC priority access for research proposals relating the SARS-CoV-2 virus
Instruct-ERIC is offering priority access to groups that need to use its structural biology services for projects directly related to COVID-19 viral proteins. Priority access will ensure a faster review of research proposals relating to COVID-19.
What to do when your grant is rejected
Losing out on a grant hurts, but don’t lose heart — average success rates are around 20% among large funders, so grant rejection is common. Discover how to bounce back, find alternative funding and boost your chances of success next time.
Revolutionary cryo-EM is taking over structural biology
The number of protein structures being determined by cryo-electron microscopy is growing at an explosive rate. A report published by Nature on February 10, 2020 says that a revolutionary technique for determining the 3D shape of biomacromolecules is booming. Last week, a database that collects protein and other molecular structures determined by cryo-electron microscopy, or cryo-EM, acquired its 10,000th entry.
Highlights of Coronavirus Structural Studies
Structural basis of SARS-CoV-2 spike protein induced by ACE2
In the preliminary paper, published in bioRxiv, Gal Marker et al. from the Institute for Immuno-oncology, Sheba Medical Center, Israel, determined the key structural changes of spike protein components induced by the receptor and characterized their intramolecular interactions. They show that κ-helix (also known as polyproline II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. They demonstrate a series of conversions between switch-like κ-helix and β-strand, and conformational variations in a set of short α-helices which affect the proximal hinge region. These conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables them to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.
Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by Remdesivir
The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a target of the antiviral drug, Remdesivir. In the Science paper (published May 1, 2020) Yechun Xu, Shuyang Zhang, Yan Zhang, and H. Eric Xu report the cryo-EM structure of the SARS-CoV-2 RdRp either in the apo form at 2.8 Å resolution or in complex with a 50-base template-primer RNA and Remdesivir at 2.5 Å resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp where Remdesivir is covalently incorporated into the primer strand at the first replicated base pair and terminates chain elongation. The obtained structures provide critical insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.
Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2
Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading around the world. There is no existing vaccine or proven drug to pre- vent infections and stop virus proliferation. Although this virus is similar to human and animal SARS-CoVs and Middle East Respiratory Syndrome coronavirus (MERS-CoVs), the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. Andrzej Joachimiak et. al applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases, Argonne National Laboratory, to produce SARS-CoV-2 proteins and structures. In the Protein Science paper they report two high-resolution crystal structures of endoribonuclease Nsp15/NendoU and compare these structures with previously reported homologs from SARS and MERS coronaviruses.
Reader's Corner Archive
Potential of cryo-EM for high-resolution structural analysis of gap junction channels
The review by Oshima et. al. in Current Opinions in Structural Biology outlines structural biology of gap junction channels utilizing crystallography and single-particle cryo-EM to shed light on the functional mechanisms of cell-cell communication that are essential for multicellular organisms.
Molecular dynamics simulations of macromolecular crystals
The paper of David Case and David Cerutti in WIREs Computational Molecular Science evaluates past fusions of simulations and crystallography and looks ahead to the ways that simulations of crystal structures will enhance structural biology in the future.
Combining Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) Spectroscopy for Integrative Structural Biology of Protein–RNA Complexes
In this publication Fred Allain et.al. reviews recent advances in hybrid structural approaches with a focus on combining MS analysis of cross-linked protein–RNA complexes and NMR spectroscopy.
Quo Vadis Biomolecular NMR Spectroscopy?
In Quo Vadis Biomolecular NMR Spectroscopy? Phil Selenko reviews recent methodological spin-off applications whose developments were stimulated by cellular NMR approaches.
Essay on Biomembrane Structure
Christoph Gerle provides historical outline of how we arrived at our current understanding of biomembranes and the models we use to describe them in Essay on Biomembrane Structure. A selection of direct experimental findings on the nano-scale structure of biomembranes is taken up to discuss their physical nature, and special emphasis is put on the surprising insights that arise from atomic scale descriptions.
Role of integrative structural biology in understanding transcriptional initiation
Role of integrative structural biology in understanding transcriptional initiation is discussed by Philip Robinson et. al. in a review, which presents a general background to integrative structural biology, describes of how it should be practically implemented, and shows how it has furthered our understanding of the biology of large transcriptional assemblies.
Frontiers in Cryo Electron Microscopy of Complex Macromolecular Assemblies
In this publication Sriram Subramaniam et. al. report on structural studies of G protein–coupled receptors, spliceosomes, and fibrillar specimens and illustrate the progress made by advanced cryo-EM methods.
The evolution of solution state NMR pulse sequences through the ‘eyes’ of triple-resonance spectroscopy
Lewis Kay in The evolution of solution state NMR pulse sequences through the ‘eyes’ of triple-resonance spectroscopy highlights how pulse sequence ‘engineering’ has evolved during past decades with the focus on liquid state NMR applications.