3cl5 | pdb_00003cl5
Structure of coronavirus hemagglutinin-esterase in complex with 4,9-O-diacetyl sialic acid
Structural highlights
Function[HEMA_CVBM] Structural protein that makes short spikes at the surface of the virus. Contains receptor binding and receptor-destroying activities. Mediates de-O-acetylation of N-acetyl-9-O-acetylneuraminic acid, which is probably the receptor determinant recognized by the virus on the surface of erythrocytes and susceptible cells. This receptor-destroying activity is important for virus release as it probably helps preventing self-aggregation and ensures the efficient spread of the progeny virus from cell to cell. May serve as a secondary viral attachment protein for initiating infection, the spike protein being the major one. Seems to be a 'luxury' protein that is not absolutely necessary for virus infection in culture. However, its presence in the virus may alter its pathogenicity. May become a target for both the humoral and the cellular branches of the immune system. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe hemagglutinin-esterases (HEs) are a family of viral envelope glycoproteins that mediate reversible attachment to O-acetylated sialic acids by acting both as lectins and as receptor-destroying enzymes (RDEs). Related HEs occur in influenza C, toro-, and coronaviruses, apparently as a result of relatively recent lateral gene transfer events. Here, we report the crystal structure of a coronavirus (CoV) HE in complex with its receptor. We show that CoV HE arose from an influenza C-like HE fusion protein (HEF). In the process, HE was transformed from a trimer into a dimer, whereas remnants of the fusion domain were adapted to establish novel monomer-monomer contacts. Whereas the structural design of the RDE-acetylesterase domain remained unaltered, the HE receptor-binding domain underwent remodeling to such extent that the ligand is now bound in opposite orientation. This is surprising, because the architecture of the HEF site was preserved in influenza A HA over a much larger evolutionary distance, a switch in receptor specificity and extensive antigenic variation notwithstanding. Apparently, HA and HEF are under more stringent selective constraints than HE, limiting their exploration of alternative binding-site topologies. We attribute the plasticity of the CoV HE receptor-binding site to evolutionary flexibility conferred by functional redundancy between HE and its companion spike protein S. Our findings offer unique insights into the structural and functional consequences of independent protein evolution after interviral gene exchange and open potential avenues to broad-spectrum antiviral drug design. Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution.,Zeng Q, Langereis MA, van Vliet AL, Huizinga EG, de Groot RJ Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9065-9. Epub 2008 Jun 11. PMID:18550812[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||||||
