2l5j

structure of the spliceosomal phosphopeptide P140 (phosphorylated form)

spinqualitylabelsall models 2l5j Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2l5j is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 8 models Ligands: SEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RU17_HUMAN Mediates the splicing of pre-mRNA by binding to the loop I region of U1-snRNA. The truncated isoforms cannot bind U1-snRNA. Publication Abstract from PubMed 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. The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.,Page N, Schall N, Strub JM, Quinternet M, Chaloin O, Decossas M, Cung MT, Van Dorsselaer A, Briand JP, Muller S PLoS One. 2009;4(4):e5273. Epub 2009 Apr 23. PMID:19390596 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoprotein 3D structures

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