4X05

Crystal structure of P domain from norovirus strain Farmington Hills 2004 in complex with HBGA type B (triglycan)

4X05 の概要

• エントリーDOI: 10.2210/pdb4x05/pdb
• 関連するPDBエントリー: 4OOV 4OPS
• 分子名称: Major capsid protein, alpha-L-fucopyranose-(1-2)-[alpha-D-galactopyranose-(1-3)]alpha-D-galactopyranose (3 entities in total)
• 機能のキーワード: viral capsid protein, protruding domain, viral protein
• 由来する生物種: Norovirus Hu/GII.4/Farmington Hills/2004/USA
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 137100.34

構造登録者

Singh, B.K.,Leuthold, M.,Hansman, G.S. (登録日: 2014-11-20, 公開日: 2014-12-17, 最終更新日: 2024-05-08)

主引用文献

Singh, B.K.,Leuthold, M.M.,Hansman, G.S.
Human noroviruses' fondness for histo-blood group antigens.
J.Virol., 89:2024-2040, 2015

PubMed Abstract: Human noroviruses are the dominant cause of outbreaks of gastroenteritis around the world. Human noroviruses interact with the polymorphic human histo-blood group antigens (HBGAs), and this interaction is thought to be important for infection. Indeed, synthetic HBGAs or HBGA-expressing enteric bacteria were shown to enhance norovirus infection in B cells. A number of studies have found a possible relationship between HBGA type and norovirus susceptibility. The genogroup II, genotype 4 (GII.4) noroviruses are the dominant cluster, evolve every other year, and are thought to modify their binding interactions with different HBGA types. Here we show high-resolution X-ray crystal structures of the capsid protruding (P) domains from epidemic GII.4 variants from 2004, 2006, and 2012, cocrystallized with a panel of HBGA types (H type 2, Lewis Y, Lewis B, Lewis A, Lewis X, A type, and B type). Many of the HBGA binding interactions were found to be complex, involving capsid loop movements, alternative HBGA conformations, and HBGA rotations. We showed that a loop (residues 391 to 395) was elegantly repositioned to allow for Lewis Y binding. This loop was also slightly shifted to provide direct hydrogen- and water-mediated bonds with Lewis B. We considered that the flexible loop modulated Lewis HBGA binding. The GII.4 noroviruses have dominated outbreaks over the past decade, which may be explained by their exquisite HBGA binding mechanisms, their fondness for Lewis HBGAs, and their temporal amino acid modifications.

PubMed: 25428879
DOI: 10.1128/JVI.02968-14

実験手法

X-RAY DIFFRACTION (1.98 Å)