1xwh
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1xwh.gif|left|200px]] | [[Image:1xwh.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1xwh", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_1xwh| PDB=1xwh | SCENE= }} | |
| - | | | + | |
| - | | | + | |
| - | }} | + | |
'''NMR structure of the first phd finger of autoimmune regulator protein (AIRE1): insights into apeced''' | '''NMR structure of the first phd finger of autoimmune regulator protein (AIRE1): insights into apeced''' | ||
| Line 33: | Line 30: | ||
[[Category: Simon, B.]] | [[Category: Simon, B.]] | ||
[[Category: Stier, G.]] | [[Category: Stier, G.]] | ||
| - | [[Category: | + | [[Category: Apeced]] |
| - | [[Category: | + | [[Category: E3 ligase]] |
| - | [[Category: | + | [[Category: Nucleosome]] |
| - | [[Category: | + | [[Category: Phd domain]] |
| - | [[Category: | + | [[Category: Zn binding domain]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:35:33 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 12:35, 3 May 2008
NMR structure of the first phd finger of autoimmune regulator protein (AIRE1): insights into apeced
Overview
Mutations in the autoimmune regulator protein AIRE1 cause a monogenic autosomal recessively inherited disease: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE1 is a multidomain protein that harbors two plant homeodomain (PHD)-type zinc fingers. The first PHD finger of AIRE1 is a mutational hot spot, to which several pathological point mutations have been mapped. Using heteronuclear NMR spectroscopy, we determined the solution structure of the first PHD finger of AIRE1 (AIRE1-PHD1), and characterized the peptide backbone mobility of the domain. We performed a conformational analysis of pathological AIRE1-PHD1 mutants that allowed us to rationalize the structural impact of APECED-causing mutations and to identify an interaction site with putative protein ligands of the AIRE1-PHD1 domain. The structure unequivocally exhibits the canonical PHD finger fold, with a highly conserved tryptophan buried inside the structure. The PHD finger is stabilized by two zinc ions coordinated in an interleaved (cross-brace) scheme. This zinc coordination resembles RING finger domains, which can function as E3 ligases in the ubiquitination pathway. Based on this fold similarity, it has been suggested that PHD fingers might also function as E3 ligases, although this hypothesis is controversial. At variance to a previous report, we could not find any evidence that AIRE1-PHD1 has an intrinsic E3 ubiquitin ligase activity, nor detect any direct interaction between AIRE1-PHD1 and its putative cognate E2. Consistently, we show that the AIRE1-PHD1 structure is clearly distinct from the RING finger fold. Our results point to a function of the AIRE1-PHD1 domain in protein-protein interactions, which is impaired in some APECED mutations.
About this Structure
1XWH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
NMR structure of the first PHD finger of autoimmune regulator protein (AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disease., Bottomley MJ, Stier G, Pennacchini D, Legube G, Simon B, Akhtar A, Sattler M, Musco G, J Biol Chem. 2005 Mar 25;280(12):11505-12. Epub 2005 Jan 13. PMID:15649886 Page seeded by OCA on Sat May 3 15:35:33 2008
Categories: Homo sapiens | Single protein | Akhtar, A. | Bottomley, M J. | Krasotkina, J. | Legube, G. | Musco, G. | Sattler, M. | Simon, B. | Stier, G. | Apeced | E3 ligase | Nucleosome | Phd domain | Zn binding domain
