2kes

From Proteopedia

(Difference between revisions)

Revision as of 08:20, 7 April 2021

Solution Structure of the Coiled-coil Domain of Synphilin-1

Structural highlights

2kes is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	SNCAIP (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SNCAP_HUMAN] Defects in SNCAIP may be a cause of Parkinson disease (PARK) [MIM:168600]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.^[1] ^[2] ^[3]

Function

[SNCAP_HUMAN] Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins. Isoform 2 inhibits autoubiquitination and proteasomal degradation of SIAH1, and thereby increases cellular levels of SIAH. Isoform 2 modulates SNCA monoubiquitination by SIAH1.^[4] ^[5]

Publication Abstract from PubMed

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.

Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication.,Xie YY, Zhou CJ, Zhou ZR, Hong J, Che MX, Fu QS, Song AX, Lin DH, Hu HY FASEB J. 2010 Jan;24(1):196-205. Epub 2009 Sep 17. PMID:19762560^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001 Oct;7(10):1144-50. PMID:11590439 doi:10.1038/nm1001-1144
↑ Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, Cookson MR, Hernandez D, Farrer MJ, Kachergus J, Engelender S, Ross CA, Berger K, Schols L, Schulz JB, Riess O, Kruger R. Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease. Hum Mol Genet. 2003 Jun 1;12(11):1223-31. PMID:12761037
↑ Myhre R, Klungland H, Farrer MJ, Aasly JO. Genetic association study of synphilin-1 in idiopathic Parkinson's disease. BMC Med Genet. 2008 Mar 21;9:19. doi: 10.1186/1471-2350-9-19. PMID:18366718 doi:10.1186/1471-2350-9-19
↑ Eyal A, Szargel R, Avraham E, Liani E, Haskin J, Rott R, Engelender S. Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5917-22. Epub 2006 Apr 4. PMID:16595633 doi:10.1073/pnas.0509707103
↑ Szargel R, Rott R, Eyal A, Haskin J, Shani V, Balan L, Wolosker H, Engelender S. Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation. J Biol Chem. 2009 Apr 24;284(17):11706-16. doi: 10.1074/jbc.M805990200. Epub 2009, Feb 17. PMID:19224863 doi:10.1074/jbc.M805990200
↑ Xie YY, Zhou CJ, Zhou ZR, Hong J, Che MX, Fu QS, Song AX, Lin DH, Hu HY. Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication. FASEB J. 2010 Jan;24(1):196-205. Epub 2009 Sep 17. PMID:19762560 doi:10.1096/fj.09-133082

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kes"

@@ Line 1: / Line 1: @@
 ==Solution Structure of the Coiled-coil Domain of Synphilin-1==
-<StructureSection load='2kes' size='340' side='right' caption='[[2kes]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<StructureSection load='2kes' size='340' side='right'caption='[[2kes]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2kes]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KES FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2kes]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KES FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNCAIP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNCAIP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kes OCA], [http://pdbe.org/2kes PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kes RCSB], [http://www.ebi.ac.uk/pdbsum/2kes PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kes ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kes OCA], [https://pdbe.org/2kes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kes RCSB], [https://www.ebi.ac.uk/pdbsum/2kes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kes ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/SNCAP_HUMAN SNCAP_HUMAN]] Defects in SNCAIP may be a cause of Parkinson disease (PARK) [MIM:[http://omim.org/entry/168600 168600]]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.<ref>PMID:11590439</ref> <ref>PMID:12761037</ref> <ref>PMID:18366718</ref>
+[[https://www.uniprot.org/uniprot/SNCAP_HUMAN SNCAP_HUMAN]] Defects in SNCAIP may be a cause of Parkinson disease (PARK) [MIM:[https://omim.org/entry/168600 168600]]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.<ref>PMID:11590439</ref> <ref>PMID:12761037</ref> <ref>PMID:18366718</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/SNCAP_HUMAN SNCAP_HUMAN]] Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins. Isoform 2 inhibits autoubiquitination and proteasomal degradation of SIAH1, and thereby increases cellular levels of SIAH. Isoform 2 modulates SNCA monoubiquitination by SIAH1.<ref>PMID:16595633</ref> <ref>PMID:19224863</ref>
+[[https://www.uniprot.org/uniprot/SNCAP_HUMAN SNCAP_HUMAN]] Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins. Isoform 2 inhibits autoubiquitination and proteasomal degradation of SIAH1, and thereby increases cellular levels of SIAH. Isoform 2 modulates SNCA monoubiquitination by SIAH1.<ref>PMID:16595633</ref> <ref>PMID:19224863</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hu, H Y]]
 [[Category: Xie, Y Y]]

2kes

From Proteopedia

Revision as of 08:20, 7 April 2021

Solution Structure of the Coiled-coil Domain of Synphilin-1

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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