2IEQ

Core Structure of S2 from the Human Coronavirus NL63 Spike Glycoprotein

2IEQ の概要

• エントリーDOI: 10.2210/pdb2ieq/pdb
• 分子名称: Spike glycoprotein, SODIUM ION, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: human coronavirus; membrane fusion; s2; virus entry; six-helix bundle, viral protein
• 由来する生物種: Human coronavirus; 詳細
• 細胞内の位置: Virion membrane ; Single-pass type I membrane protein : Q6Q1S2
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35296.96

構造登録者

Liu, J. (登録日: 2006-09-19, 公開日: 2007-01-09, 最終更新日: 2023-08-30)

主引用文献

Zheng, Q.,Deng, Y.,Liu, J.,Hoek, L.V.,Berkhout, B.,Lu, M.
Core Structure of S2 from the Human Coronavirus NL63 Spike Glycoprotein
Biochemistry, 45:15205-15215, 2006

PubMed Abstract: Human coronavirus NL63 (HCoV-NL63) has recently been identified as a causative agent of acute respiratory tract illnesses in infants and young children. The HCoV-NL63 spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This viral entry process is a primary target for vaccine and drug development. HCoV-NL63 S is expressed as a single-chain glycoprotein and consists of an N-terminal receptor-binding domain (S1) and a C-terminal transmembrane fusion domain (S2). The latter contains two highly conserved heptad-repeat (HR) sequences that are each extended by 14 amino acids relative to those of the SARS coronavirus or the prototypic murine coronavirus, mouse hepatitis virus. Limited proteolysis studies of the HCoV-NL63 S2 fusion core identify an alpha-helical domain composed of a trimer of the HR segments N57 and C42. The crystal structure of this complex reveals three C42 helices entwined in an oblique and antiparallel manner around a central triple-stranded coiled coil formed by three N57 helices. The overall geometry comprises distinctive high-affinity conformations of interacting cross-sectional layers of the six helices. As a result, this structure is unusually stable, with an apparent melting temperature of 78 degrees C in the presence of the denaturant guanidine hydrochloride at 5 M concentration. The extended HR regions may therefore be required to prime the group 1 S glycoproteins for their fusion-activating conformational changes during viral entry. Our results provide an initial basis for understanding an intriguing interplay between the presence or absence of proteolytic maturation among the coronavirus groups and the membrane fusion activity of their S glycoproteins. This study also suggests a potential strategy for the development of improved HCoV-NL63 fusion inhibitors.

PubMed: 17176042
DOI: 10.1021/bi061686w

実験手法

X-RAY DIFFRACTION (1.747 Å)