2L5I
structure of the spliceosomal phosphopeptide P140 (non-phosphorylated form)
Summary for 2L5I
| Entry DOI | 10.2210/pdb2l5i/pdb |
| Related | 2L5J |
| Descriptor | U1 small nuclear ribonucleoprotein 70 kDa (1 entity in total) |
| Functional Keywords | phosphorylation, hsc70, lupus, splicing |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: P08621 |
| Total number of polymer chains | 1 |
| Total formula weight | 2565.01 |
| Authors | Quinternet, M.,Page, N.,Schall, N.,Strub, J.,Chaloin, O.,Decossas, M.,Cung, M.,van Dorsselaer, A.,Briand, J.,Muller, S. (deposition date: 2010-11-02, release date: 2010-12-01, Last modification date: 2024-05-01) |
| Primary citation | 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 Cited by 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: 19390596DOI: 10.1371/journal.pone.0005273 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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