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Structure of Met30 variant of transthyretin and its amyloidogenic implications.

1993; Springer Nature; Volume: 12; Issue: 2 Linguagem: Inglês

10.1002/j.1460-2075.1993.tb05707.x

1460-2075

C. J. Terry, Ana M. Damas, Pedro de Oliveira, Maria João Saraiva, Isabel L. Alves, Paulo Costa, Pedro M. Matias, Yoshiyuki Sakaki, C. C. F. Blake,

Protein Kinase Regulation and GTPase Signaling

Research Article1 February 1993free access Structure of Met30 variant of transthyretin and its amyloidogenic implications. C.J. Terry C.J. Terry Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author A.M. Damas A.M. Damas Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author P. Oliveira P. Oliveira Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author M.J. Saraiva M.J. Saraiva Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author I.L. Alves I.L. Alves Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author P.P. Costa P.P. Costa Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author P.M. Matias P.M. Matias Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author Y. Sakaki Y. Sakaki Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author C.C. Blake C.C. Blake Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author C.J. Terry C.J. Terry Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author A.M. Damas A.M. Damas Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author P. Oliveira P. Oliveira Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author M.J. Saraiva M.J. Saraiva Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author I.L. Alves I.L. Alves Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author P.P. Costa P.P. Costa Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author P.M. Matias P.M. Matias Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author Y. Sakaki Y. Sakaki Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author C.C. Blake C.C. Blake Laboratory of Molecular Biophysics, University of Oxford, UK. Search for more papers by this author Author Information C.J. Terry1, A.M. Damas1, P. Oliveira1, M.J. Saraiva1, I.L. Alves1, P.P. Costa1, P.M. Matias1, Y. Sakaki1 and C.C. Blake1 1Laboratory of Molecular Biophysics, University of Oxford, UK. The EMBO Journal (1993)12:735-741https://doi.org/10.1002/j.1460-2075.1993.tb05707.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant hereditary type of lethal amyloidosis involving single (or double) amino acid substitutions in the amyloidogenic protein transthyretin (TTR). The most common type of FAP (Type I, or Portuguese) is characterized by a Val-->Met substitution at position 30. The Met30 variant of TTR has been produced by recombinant methods, crystallized in a form isomorphous with native TTR, subjected to X-ray analysis and compared structurally with the wild-type protein. The comparison shows that the effect of the substitution at position 30 is transmitted through the protein core to Cys10, the only thiol group in the TTR subunit, which becomes slightly more exposed. The variant TTR molecule is otherwise in a near-native state. Use of computer graphics has shown that it is possible to model a linear aggregate of TTR molecules, each linked to the next by a pair of disulphide bonds involving Cys10 residues. Formation of these disulphide bonds involves a small number of slightly short molecular contacts with native TTR molecules, most of which are relieved in the Met30 variant. We propose this model as a possible basis for a molecular description of the FAP amyloid fibrils. Previous ArticleNext Article Volume 12Issue 21 February 1993In this issue RelatedDetailsLoading ...