1ijn
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= TTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1iii|1III]], [[1iik|1IIK]], [[1iim|1IIM]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ijn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ijn OCA], [http://www.ebi.ac.uk/pdbsum/1ijn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ijn RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Amyloidosis, senile systemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Carpal tunnel syndrome, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Dystransthyretinemic hyperthyroxinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Olofsson, A.]] | [[Category: Olofsson, A.]] | ||
[[Category: Sauer-Eriksson, A E.]] | [[Category: Sauer-Eriksson, A E.]] | ||
| - | [[Category: BME]] | ||
[[Category: beta barrel]] | [[Category: beta barrel]] | ||
[[Category: greek key]] | [[Category: greek key]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:20:45 2008'' |
Revision as of 18:20, 30 March 2008
| |||||||
| , resolution 1.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | TTR (Homo sapiens) | ||||||
| Related: | 1III, 1IIK, 1IIM
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the transthyretin mutant TTR C10A/Y114C
Contents |
Overview
The Tyr114Cys substitution in the human plasma protein transthyretin leads to a particularly aggressive form of familial amyloidotic polyneuropathy. In a previous study we demonstrated that ATTR Tyr114Cys forms intermolecular disulfide bonds, which partly impair fibril formation and result in a more amorphous morphology. Apart from the introduced cysteinyl group in position 114, the native sequence contains one cysteine located at position 10. To deduce the role of intermolecular disulfide bridging in fibril formation we generated and characterized the TTR Cys10Ala/Tyr114Cys double mutant. Our results suggest that an intermolecular cysteine bridge at position 114 enhances the exposure of cysteine 10, thereby facilitating additional intermolecular cysteine assemblies. We also purified a disulfide-linked dimeric form of TTR Cys10Ala/Tyr114Cys, which was recognized by the anti-TTR amyloid-specific monoclonal antibody MAb (39-44). Moreover, this dimeric molecule can form protofibrils indistinguishable from the fibrils formed under reducing conditions, as judged by atomic force microscopy. Assuming that both molecules of the dimer are part of the core of the fibril, the assembly is incompatible with a preserved native or near-native dimeric interphase. Our findings raise the question of whether TTR-amyloid architecture is indeed the result of one highly stringent assembly of structures or if different fibrils may be built from different underlying structures.
Disease
Known disease associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]
About this Structure
1IJN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Cys114-linked dimers of transthyretin are compatible with amyloid formation., Karlsson A, Olofsson A, Eneqvist T, Sauer-Eriksson AE, Biochemistry. 2005 Oct 4;44(39):13063-70. PMID:16185074
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