3CL4

Crystal structure of bovine coronavirus hemagglutinin-esterase

3CL4 の概要

• エントリーDOI: 10.2210/pdb3cl4/pdb
• 関連するPDBエントリー: 1FLC 3CL5
• 分子名称: Hemagglutinin-esterase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: sgnh-hydrolase fold, swiss roll, envelope protein, glycoprotein, hemagglutinin, membrane, transmembrane, virion, hydrolase
• 由来する生物種: Bovine coronavirus (strain Mebus)
• 細胞内の位置: Virion membrane; Single-pass type I membrane protein (Potential): P15776
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44215.77

構造登録者

Zeng, Q.H.,Langereis, M.A.,van Vliet, A.L.W.,Huizinga, E.G.,de Groot, R.J. (登録日: 2008-03-18, 公開日: 2008-06-03, 最終更新日: 2024-10-16)

主引用文献

Zeng, Q.,Langereis, M.A.,van Vliet, A.L.,Huizinga, E.G.,de Groot, R.J.
Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution.
Proc.Natl.Acad.Sci.Usa, 105:9065-9069, 2008

PubMed Abstract: The 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.

PubMed: 18550812
DOI: 10.1073/pnas.0800502105

実験手法

X-RAY DIFFRACTION (2.1 Å)