2KES
Solution Structure of the Coiled-coil Domain of Synphilin-1
Summary for 2KES
| Entry DOI | 10.2210/pdb2kes/pdb |
| NMR Information | BMRB: 16156 |
| Descriptor | Synphilin-1 (1 entity in total) |
| Functional Keywords | synphillin, coiled-coil, ank repeat, disease mutation, parkinson disease, phosphoprotein, polymorphism, ubl conjugation, protein binding |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: Q9Y6H5 |
| Total number of polymer chains | 1 |
| Total formula weight | 5371.14 |
| Authors | Xie, Y.Y.,Zhou, C.J.,Zhou, Z.R.,Hu, H.Y. (deposition date: 2009-02-02, release date: 2009-02-24, Last modification date: 2024-05-29) |
| Primary citation | Xie, Y.Y.,Zhou, C.J.,Zhou, Z.R.,Hong, J.,Che, M.X.,Fu, Q.S.,Song, A.X.,Lin, D.H.,Hu, H.Y. Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication. Faseb J., 24:196-205, 2010 Cited by PubMed Abstract: alpha-Synuclein (alpha-Syn) is the major component of Lewy bodies (LBs) deposited in the brains of patients with Parkinson's disease. Synphilin-1 (Sph1) is a novel alpha-Syn-interacting protein also present in the LBs. However, the roles of alpha-Syn-Sph1 interaction in LB formation and in the related pathogenesis are still unclear. We have studied the interaction between alpha-Syn and Sph1 by biochemical and structural approaches and found that the central coiled-coil domain of Sph1 specifically interacts with the N-terminal stretch of alpha-Syn. When overexpressed in HEK 293T cells, Sph1 forms inclusions together with alpha-Syn, but the Sph1-positive inclusions cannot recruit the N-terminally truncated alpha-Syn. The central portion of Sph1 can also recruit alpha-Syn and induce inclusion formation through its coiled-coil domain. These observations demonstrate that the alpha-Syn-Sph1 interaction significantly promotes the formation of cytoplasmic alpha-Syn inclusions, which may have implications for LB formation in neural cells. We have also elucidated solution structure of the coiled-coil domain of Sph1 and its interaction with the N-terminal peptide of alpha-Syn. The specific interaction between alpha-Syn and Sph1 provides mechanistic insights into the inclusion-body formation in cells and pathological implication in Parkinson's disease. PubMed: 19762560DOI: 10.1096/fj.09-133082 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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