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.
Registration for Advanced methods in macromolecular crystallization IX is now open
Proposed deadline for applications for this course which is focused on theoretical aspects of crystal growth process as well as practical work is March 20th 2020.
Highlights of Coronavirus Structural Studies
Controlling the SARS-CoV-2 Spike Glycoprotein Conformation
The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. In the bioRcin paper, to better understand S-protein mobility, a structure-based vector analysis of available β-CoV S-protein structures was implemented. Rory Henderson, Priyamvada Acharya et.al. from Duke Human Vaccine Institute, Durham, USA found that despite overall similarity in domain organization, different β-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs ‘down’ position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs ‘up’ configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications.
Distinct conformational states of SARS-CoV-2 spike protein
The ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has created urgent needs for intervention strategies to control the crisis. The spike (S) protein of the virus forms a trimer and catalyzes fusion between viral and target cell membranes - the first key step of viral infection. Bing Chen et. al. report two cryo-EM structures, both derived from a single preparation of the full-length S protein, representing the prefusion (3.1Å resolution) and postfusion (3.3Å resolution) conformations, respectively. The spontaneous structural transition to the postfusion state under mild conditions is independent of target cells. The prefusion trimer forms a tightly packed structure with three receptor-binding domains clamped down by a segment adjacent to the fusion peptide, significantly different from recently published structures of a stabilized S ectodomain trimer. The postfusion conformation is a rigid tower-like trimer, but decorated by N-linked glycans along its long axis with almost even spacing, suggesting possible involvement in a mechanism protecting the virus from host immune responses and harsh external conditions. These findings advance understanding of how SARS-CoV-2 enters a host cell and may guide development of vaccines and therapeutics.
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.
Reader's Corner Archive
Visualization of biological macromolecules at near-atomic resolution: cryo-electron microscopy comes of age
The topical review by Alok K. Mitra recapitulates developments and transformational advances of cryo-EM technology.
The expanding toolkit for structural biology: synchrotrons, X-ray lasers and cryo-EM
Samar Hasnain et. al. describe the steadily-expanding methodologies for atomic resolution studies in The expanding toolkit for structural biology: synchrotrons, X-ray lasers and cryo-EM. Of note is the following statistics: Despite the wealth of structures in the Protein Data Bank, a closer examination reveals that 89% of the structures, i.e. 126 994, are of proteins or complexes with a molecular weight of less than 160 kDa. Furthermore, only 4% of the deposited structures have a molecular weight in excess of 300 kDa.