4XFO: Structure Of An Amyloid-forming Segment Tavvtn From Human Transthyretin

The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, we designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
PDB ID: 4XFODownload
MMDB ID: 133495
PDB Deposition Date: 2014/12/27
Updated in MMDB: 2015/12
Experimental Method:
x-ray diffraction
Resolution: 1.35  Å
Source Organism:
Similar Structures:
Biological Unit for 4XFO: monomeric; determined by author
Molecular Components in 4XFO
Label Count Molecule
Protein (1 molecule)
Amyloid-forming Peptide Tavvtn
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB