5TTR

LEU 55 PRO TRANSTHYRETIN CRYSTAL STRUCTURE

Summary for 5TTR

• Entry DOI: 10.2210/pdb5ttr/pdb
• Descriptor: TRANSTHYRETIN (1 entity in total)
• Functional Keywords: transthyretin, amyloid, fap, thyroxine, transport
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 8
• Total formula weight: 110090.54

Authors

Sebastiao, M.P.,Saraiva, M.J.,Damas, A.M. (deposition date: 1998-04-30, release date: 1999-06-01, Last modification date: 2024-05-22)

Primary citation

Sebastiao, M.P.,Saraiva, M.J.,Damas, A.M.
The crystal structure of amyloidogenic Leu55 --> Pro transthyretin variant reveals a possible pathway for transthyretin polymerization into amyloid fibrils.
J.Biol.Chem., 273:24715-24722, 1998

PubMed Abstract: The x-ray crystal structure of the amyloidogenic Leu55 --> Pro transthyretin (TTR) variant, implicated as the causative agent in early-onset familial amyloidotic polyneuropathy (Jacobson, D. R., McFarlin, D. E., Kane, I., and Buxbaum, J. N. (1992) Hum. Genet. 89, 353-356), has been solved by molecular replacement, refined at 2.7 A to a Rcryst value of 0.190 (Fobs > 2.0sigma), and compared with wild-type transthyretin to understand the molecular mechanism(s) involved in amyloidogenesis. Leu55 --> Pro TTR crystallizes in space group C2, with eight monomers in the asymmetric unit, and the observed packing contacts are considerably different from those described for the wild-type protein. Refinement of the crystal structure shows that the proline for leucine substitution disrupts the hydrogen bonds between strands D and A, resulting in different interface contacts. Based on the assumption that the observed packing contacts may be significant for amyloidogenesis, a model for the TTR amyloid is proposed. It consists of a tubular structure with inner and outer diameters approximately of 30 and 100 A and four monomers per cross-section.

PubMed: 9733771
DOI: 10.1074/jbc.273.38.24715

Experimental method

X-RAY DIFFRACTION (2.7 Å)