4C3E

HRSV M2-1 mutant S58D S61D, P21 crystal

4C3E の概要

• エントリーDOI: 10.2210/pdb4c3e/pdb
• 関連するPDBエントリー: 4C3B 4C3D
• 分子名称: MATRIX M2-1, ZINC ION (3 entities in total)
• 機能のキーワード: viral protein
• 由来する生物種: HUMAN RESPIRATORY SYNCYTIAL VIRUS
• 細胞内の位置: Virion (Potential): P04545
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 363571.33

構造登録者

Tanner, S.J.,Ariza, A.,Richard, C.A.,Wu, W.,Trincao, J.,Hiscox, J.A.,Carroll, M.W.,Silman, N.J.,Eleouet, J.F.,Edwards, T.A.,Barr, J.N. (登録日: 2013-08-22, 公開日: 2014-01-22, 最終更新日: 2024-05-08)

主引用文献

Tanner, S.J.,Ariza, A.,Richard, C.,Kyle, H.F.,Dods, R.L.,Blondot, M.,Wu, W.,Trincao, J.,Trinh, C.H.,Hiscox, J.A.,Carroll, M.W.,Silman, N.J.,Eleouet, J.,Edwards, T.A.,Barr, J.N.
Crystal Structure of the Essential Transcription Antiterminator M2-1 Protein of Human Respiratory Syncytial Virus and Implications of its Phosphorylation.
Proc.Natl.Acad.Sci.USA, 111:1580-, 2014

PubMed Abstract: The M2-1 protein of the important pathogen human respiratory syncytial virus is a zinc-binding transcription antiterminator that is essential for viral gene expression. We present the crystal structure of full-length M2-1 protein in its native tetrameric form at a resolution of 2.5 Å. The structure reveals that M2-1 forms a disk-like assembly with tetramerization driven by a long helix forming a four-helix bundle at its center, further stabilized by contact between the zinc-binding domain and adjacent protomers. The tetramerization helix is linked to a core domain responsible for RNA binding activity by a flexible region on which lie two functionally critical serine residues that are phosphorylated during infection. The crystal structure of a phosphomimetic M2-1 variant revealed altered charge density surrounding this flexible region although its position was unaffected. Structure-guided mutagenesis identified residues that contributed to RNA binding and antitermination activity, revealing a strong correlation between these two activities, and further defining the role of phosphorylation in M2-1 antitermination activity. The data we present here identify surfaces critical for M2-1 function that may be targeted by antiviral compounds.

PubMed: 24434552
DOI: 10.1073/PNAS.1317262111

実験手法

X-RAY DIFFRACTION (2.4 Å)