3SSG
Structure of transthyretin L55P in complex with Zn
Summary for 3SSG
| Entry DOI | 10.2210/pdb3ssg/pdb |
| Descriptor | Transthyretin, ZINC ION, CACODYLATE ION, ... (4 entities in total) |
| Functional Keywords | amyloid, transthyretin, hormone |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: P02766 |
| Total number of polymer chains | 1 |
| Total formula weight | 14029.12 |
| Authors | Castro-Rodrigues, A.F.,Gales, L.,Damas, A.M. (deposition date: 2011-07-08, release date: 2011-11-30, Last modification date: 2024-02-28) |
| Primary citation | Castro-Rodrigues, A.F.,Gales, L.,Saraiva, M.J.,Damas, A.M. Structural insights into a zinc-dependent pathway leading to Leu55Pro transthyretin amyloid fibrils. Acta Crystallogr.,Sect.D, 67:1035-1044, 2011 Cited by PubMed Abstract: Human transthyretin (TTR) is a homotetrameric protein that is responsible for the formation of amyloid in patients with familiar amyloidotic polyneuropathy (FAP), familiar amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA). Amyloid fibrils are characterized by a cross-β structure. However, details of how TTR monomers are organized to form such an assembly remain unknown. The effect of Zn(2+) in increasing TTR L55P amyloidogenecity has been reported. Crystals of the TTR L55P-Zn(2+) complex were grown under conditions similar to those leading to higher amyloidogenic potential of the variant protein and the three-dimensional structure of the complex was determined by X-ray crystallography. Two different tetrahedral Zn(2+)-binding sites were identified: one cross-links two tetramers, while the other lies at the interface between two monomers in a dimer. The association of monomers involving the two Zn(2+)-binding sites leads to a bidimensional array with a cross-β structure. The formation of this structure and subsequent organization into amyloid fibrils was monitored by fluorescence spectroscopy and electron microscopy. The TTR L55P-Zn(2+) structure offers the first molecular insights into the role of Zn(2+) as a mediator of cross-β-type structure in TTR amyloidosis and the relevance of a Zn(2+)-dependent pathway leading to the production of early amyloidogenic intermediates is discussed. PubMed: 22120741DOI: 10.1107/S090744491104491X PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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