2L5J

structure of the spliceosomal phosphopeptide P140 (phosphorylated form)

2L5J の概要

• エントリーDOI: 10.2210/pdb2l5j/pdb
• 関連するPDBエントリー: 2L5I
• 分子名称: U1 small nuclear ribonucleoprotein 70 kDa (1 entity in total)
• 機能のキーワード: phosphorylation, hsc70, lupus, splicing
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P08621
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2644.99

構造登録者

Quinternet, M.,Page, N.,Schall, N.,Strub, J.,Chaloin, O.,Decossas, M.,Cung, M.,van Dorsselaer, A.,Briand, J.,Muller, S. (登録日: 2010-11-02, 公開日: 2010-12-01, 最終更新日: 2024-11-06)

主引用文献

Page, N.,Schall, N.,Strub, J.M.,Quinternet, M.,Chaloin, O.,Decossas, M.,Cung, M.T.,Van Dorsselaer, A.,Briand, J.P.,Muller, S.
The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
Plos One, 4:e5273-e5273, 2009

PubMed Abstract: The phosphopeptide P140 issued from the spliceosomal U1-70K snRNP protein is recognized by lupus CD4(+) T cells, transiently abolishes T cell reactivity to other spliceosomal peptides in P140-treated MRL/lpr mice, and ameliorates their clinical features. P140 modulates lupus patients' T cell response ex vivo and is currently included in phase IIb clinical trials. Its underlying mechanism of action remains elusive. Here we show that P140 peptide binds a unique cell-surface receptor, the constitutively-expressed chaperone HSC70 protein, known as a presenting-protein. P140 induces apoptosis of activated MRL/lpr CD4(+) T cells. In P140-treated mice, it increases peripheral blood lymphocyte apoptosis and decreases B cell, activated T cell, and CD4(-)CD8(-)B220(+) T cell counts via a specific mechanism strictly depending on gammadelta T cells. Expression of inflammation-linked genes is rapidly regulated in CD4(+) T cells. This work led us to identify a powerful pathway taken by a newly-designed therapeutic peptide to immunomodulate lupus autoimmunity.

PubMed: 19390596
DOI: 10.1371/journal.pone.0005273

実験手法

SOLUTION NMR