The human coronavirus HCoV-229E S-protein structure and receptor binding

By Zhijie Li, A. Tomlinson, A. Wong, Dongxia Zhou, M. Desforges, P. Talbot, S. Benlekbir, John L. Rubinstein, J. Rini. 2019

198 citations recorded by the source corpus.

The coronavirus S-protein mediates receptor binding and fusion of the viral and host cell membranes. In HCoV-229E, its receptor binding domain (RBD) shows extensive sequence variation but how S-protein function is maintained is not understood. Reported are the X-ray crystal structures of Class III-V RBDs in complex with human aminopeptidase N (hAPN), as well as the electron cryomicroscopy structure of the 229E S-protein. The structures show that common core interactions define the specificity for hAPN and that the peripheral RBD sequence variation is accommodated by loop plasticity. The results provide insight into immune evasion and the cross-species transmission of 229E and related coronaviruses. We also find that the 229E S-protein can expose a portion of its helical core to solvent. This is undoubtedly facilitated by hydrophilic subunit interfaces that we show are conserved among coronaviruses. These interfaces likely play a role in the S-protein conformational changes associated with membrane fusion.

Subfields: Animal Science and Zoology, Epidemiology, Infectious Diseases

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Animal Science and Zoology

1. D. Veesler
2. A. Walls
3. M. A. Tortorici

In Epidemiology

1. M. A. Tortorici
2. Jesse D. Bloom
3. A. Walls
4. D. Veesler

In Infectious Diseases

1. D. Veesler
2. A. Walls
3. M. A. Tortorici
4. Andrew T. McGuire
5. A. Wall
6. Young-Jun Park
7. Jesse D. Bloom

Citations in the corpus

• Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, background): “, 2009), trimer opening is also expected to occur to expose their RBMs that are otherwise buried at the interface between protomers in the closed S trimers (Li et al., 2019; Walls et al., 2016b).”
• Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 (2020, unknown): “HCoV-229E binds to human aminopeptidase N (hAPN) (Li et al., 2019), and MERS-CoV interacts with human dipeptidyl peptidase 4 (hDPP4 or hCD26) (Lu et al.”
• A human coronavirus evolves antigenically to escape antibody immunity (2020, background): “Coronavirus spikes consist of two subunits, S1 and S2, and it is well known that S2 is relatively conserved whereas S1 is more rapidly evolving (Liò and Goldman, 2004; Tortorici and Veesler, 2019).”
• Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies (2020, unknown): “Nevertheless, the 3D structures of S protein trimer ectodomains are similar to each other and to other coronavirus S structures, including the finding of flexible RBDs (S1 domains) that can be in various ‘‘up’’ conformations or in the ‘‘down’’ conformation of the closed pre-fusion trimer (Kirchdoerf”