1h6e: Difference between revisions
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'''MU2 ADAPTIN SUBUNIT (AP50) OF AP2 ADAPTOR (SECOND DOMAIN), COMPLEXED WITH CTLA-4 INTERNALIZATION PEPTIDE TTGVYVKMPPT''' | {{Structure | ||
|PDB= 1h6e |SIZE=350|CAPTION= <scene name='initialview01'>1h6e</scene>, resolution 3.60Å | |||
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'''MU2 ADAPTIN SUBUNIT (AP50) OF AP2 ADAPTOR (SECOND DOMAIN), COMPLEXED WITH CTLA-4 INTERNALIZATION PEPTIDE TTGVYVKMPPT''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1H6E is a [ | 1H6E is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H6E OCA]. | ||
==Reference== | ==Reference== | ||
Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28., Follows ER, McPheat JC, Minshull C, Moore NC, Pauptit RA, Rowsell S, Stacey CL, Stanway JJ, Taylor IW, Abbott WM, Biochem J. 2001 Oct 15;359(Pt 2):427-34. PMID:[http:// | Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28., Follows ER, McPheat JC, Minshull C, Moore NC, Pauptit RA, Rowsell S, Stacey CL, Stanway JJ, Taylor IW, Abbott WM, Biochem J. 2001 Oct 15;359(Pt 2):427-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11583591 11583591] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:32:51 2008'' | ||
Revision as of 12:32, 20 March 2008
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MU2 ADAPTIN SUBUNIT (AP50) OF AP2 ADAPTOR (SECOND DOMAIN), COMPLEXED WITH CTLA-4 INTERNALIZATION PEPTIDE TTGVYVKMPPT
OverviewOverview
The medium chain mu 2 subunit (AP50) of the clathrin-associated adapter protein complex 2 (AP-2) interacts specifically with the tyrosine-based signals of several integral membrane proteins through the consensus sequence YXXPhi, where X can be any residue and Phi is a large hydrophobic residue. Using surface plasmon resonance combined with structural information, we have analysed the interaction of AP50 with peptides derived from the cytoplasmic tail of cytotoxic T-lymphocyte antigen 4 (CTLA-4). The crystal structure of AP50 in complex with a CTLA-4-derived peptide was determined to 3.6 A (1 A=0.1 nm) resolution. The binding domain of AP50 (residues 164-435) was expressed in Escherichia coli and purified. In agreement with previous reports, the AP50 domain bound to residues 152-174 of CTLA-4, but not to the same peptide that was phosphorylated at the single tyrosine residue (position 165). The interaction exhibited fast kinetics with rapid on and off rates and a K(d) of 0.7 microM. In order to further understand why AP50 binds to CTLA-4, but not to the homologous receptor CD28, a comparison of binding of AP50 with five peptides with single changes in and around the YXXPhi motif to the equivalent residues of CD28 was made. T162H greatly reduced binding, whereas T161L had little effect. Mutations G163S, V164D and K167N all exhibited reduced binding. Modelling of the single amino acid changes using structural information, was in broad agreement with the binding data, demonstrating that residues outside of the YXXPhi motif are also important in the interaction of membrane proteins with AP50.
DiseaseDisease
Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[123890], Diabetes mellitus, insulin-dependent, susceptibility to OMIM:[123890], Graves disease, susceptibility to OMIM:[123890], Hypothyroidism, autoimmune OMIM:[123890]
About this StructureAbout this Structure
1H6E is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28., Follows ER, McPheat JC, Minshull C, Moore NC, Pauptit RA, Rowsell S, Stacey CL, Stanway JJ, Taylor IW, Abbott WM, Biochem J. 2001 Oct 15;359(Pt 2):427-34. PMID:11583591
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