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.
Instruct-ERIC Training call now open
Call for proposals for Instruct Centre Training Courses to be held in 2020 is now open.
CIISB 2020 - A Short Outlook into the Foreseeable Future in 6654 Characters
On January 31, 2020 CIISB has submitted the final report of the MEYS large infrastructure support project LM 2015043, which financed its operation during the years 2016-2019. The final report contains also a short description and outlook of the CIISB activities in the upcoming period.
Highlights of Coronavirus Structural Studies
Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome– coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. The Science article by Qiang Zhou et. al. presents cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain
of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.
Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome– coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, also called 3CLpro) because of its essential role in processing the polyproteins that are translated from the viral RNA. Rolf Hingenfeld et. al. report in Science the x-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an a-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, they developed the lead compound into a potent inhibitor of the SARS-CoV-2 Mpro. The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. In the study published in Cell, David Veesler with coworkers determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, they demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
Reader's Corner Archive
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.
Principles for Integrative Structural Biology Studies
Guru of integrative structural biology computation Andrej Sali and Michale P. Rout summarize in the recent Cell Primer Principles for Integrative Structural Biology Studies.
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.