PDBsum entry 3djz

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protein Protein-protein interface(s) links
Transport protein PDB id
Protein chain
116 a.a. *
Waters ×126
* Residue conservation analysis
PDB id:
Name: Transport protein
Title: Crystal structure of transthyretin variant l55p at neutral p
Structure: Transthyretin. Chain: a, b. Synonym: prealbumin, tbpa, ttr, attr. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.82Å     R-factor:   0.197     R-free:   0.219
Authors: L.Cendron,G.Zanotti,C.Folli,R.Berni
Key ref: L.Cendron et al. (2009). Amyloidogenic potential of transthyretin variants: insights from structural and computational analyses. J Biol Chem, 284, 25832-25841. PubMed id: 19602727
24-Jun-08     Release date:   14-Jul-09    
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Protein chains
Pfam   ArchSchema ?
P02766  (TTHY_HUMAN) -  Transthyretin
147 a.a.
116 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     transport   5 terms 
  Biochemical function     protein binding     5 terms  


J Biol Chem 284:25832-25841 (2009)
PubMed id: 19602727  
Amyloidogenic potential of transthyretin variants: insights from structural and computational analyses.
L.Cendron, A.Trovato, F.Seno, C.Folli, B.Alfieri, G.Zanotti, R.Berni.
Human transthyretin (TTR) is an amyloidogenic protein whose mild amyloidogenicity is enhanced by many point mutations affecting considerably the amyloid disease phenotype. To ascertain whether the high amyloidogenic potential of TTR variants may be explained on the basis of the conformational change hypothesis, an aim of this work was to determine structural alterations for five amyloidogenic TTR variants crystallized under native and/or destabilizing (moderately acidic pH) conditions. While at acidic pH structural changes may be more significant because of a higher local protein flexibility, only limited alterations, possibly representing early events associated with protein destabilization, are generally induced by mutations. This study was also aimed at establishing to what extent wild-type TTR and its amyloidogenic variants are intrinsically prone to beta-aggregation. We report the results of a computational analysis predicting that wild-type TTR possesses a very high intrinsic beta-aggregation propensity which is on average not enhanced by amyloidogenic mutations. However, when located in beta-strands, most of these mutations are predicted to destabilize the native beta-structure. The analysis also shows that rat and murine TTR have a lower intrinsic beta-aggregation propensity and a similar native beta-structure stability compared with human TTR. This result is consistent with the lack of in vitro amyloidogenicity found for both murine and rat TTR. Collectively, the results of this study support the notion that the high amyloidogenic potential of human pathogenic TTR variants is determined by the destabilization of their native structures, rather than by a higher intrinsic beta-aggregation propensity.