23. May 2017

Towards understanding of human betacoronavirus HKU1 life cycle

Researchers from China and USA join forces with Swiss Light Source (SLS) macromolecular crystallography (MX) beamline scientists in a study, which aims at understanding an important step in the life cycle of the human betacoronavirus HKU1.

Coronaviruses are positive single-stranded RNA viruses, which cause significant percentage of acute respiratory illnesses in humans. In recent years SARS and MERS were responsible for two pandemics of deadly pneumonia. Currently, there is no vaccines or specific antiviral treatment available against coronaviruses. Structural characterization of proteins essential in virus life cycle provides valid functional information and is basis for structure-based drug design. Recent publication on human coronavirus HKU1 including structure determination of the protein S1, which binds to yet unknown human receptor and initiates virus entry into host, brings possibility of finding effective treatment against coronavirus closer [1].

Human coronavirus HKU1 is a pathogen causing acute respiratory illness. HKU1 infection generally results in mild 
upper respiratory tract disease, but can occasionally cause severe respiratory diseases 
including pneumonia in very young children, the elderly, and immunocompromised 
patients. Research published in Nature Communications [1] was assisted by SLS beamline scientists Justyna Wojdyla and Meitian Wang, who applied an experimental phasing technique called native-SAD to fully exploit the unique features of the SLS MX beamline X06DA [2,3]. This phasing method enabled de novo structure determination of native S1 protein without additional labeling. Native-SAD is particularly convenient for viral proteins produced in sophisticated eukaryotic expression systems, where introduction of non-standard amino acids, such as selenomethionine, is tedious or not possible. Structural characterization of HKU1 S1 protein contributed to better understanding of entry, immunity and evolution of coronavirus S proteins and allowed determination of residues critical for receptor binding and neutralizing antibody binding.

Prof. Dr. Sheng Cui, MOH Key Laboratory of Systems Biology of Pathogens
Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Phone: +86 1067828669, e-mail: cui.sheng@ipbcams.ac.cn

Dr. Justyna Wojdyla, Swiss Light Source
Paul Scherrer Institut, 5232 Villigen PSI, Switzerland
Phone: +41 56 310 5428, e-mail: justyna.wojdyla@psi.ch

Dr. Meitian Wang, Swiss Light Source
Paul Scherrer Institut, 5232 Villigen PSI, Switzerland
Phone: +41 56 310 4175, e-mail: meitian.wang@psi.ch

Original Publication
1. Crystal Structure of the Receptor Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1
Ou X, Guan H, Qin B, Mu Z, Wojdyla J, Wang M, Dominguez SR, Qian Z, Cui S
Nature Communications, 8:15216, 2017
DOI: 10.1038/ncomms15216
Additional literature
2. Fast native SAD phasing for routine macromolecular structure determination
Weinert T, Olieric V, Waltersperger S, Panepucci E, Chen L, Zhang H, Zhou D, Rose J, Ebihara A, Kuramitsu S, Li D, Howe N, Schnapp G, Pautsch A, Bargsten K, Prota A, Surana P, Kottur J, Nair D, Basilico F, Cecatiello V, Pasqualato S, Boland A, Weichenrieder O, Wang BC, Steinmetz M, Caffrey M, Wang M
Nature Methods, 12(2):131-3, 2015
DOI: 10.1038/nmeth.3211

3. PRIGo: a new multi-axis goniometer for macromolecular crystallography
Waltersperger S, Olieric V, Pradervand C, Glettig W, Salathe M, Fuchs M.R, Curtin A, Wang X, Ebner S, Panepucci E, Weinert T, Schulze-Briese C, Wang M
Journal of Synchrotron Radiation, 22(Pt 4):895-900, 2015
DOI: 10.1107/S1600577515005354