Structure of Monomeric Transthyretin Carrying the Clinically Important T119M Mutation
Dr. Jin Hae Kim
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Von-Siebold-Strasse 3a, 37075 Göttingen, Germany
Search for more papers by this authorDr. Javier Oroz
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Von-Siebold-Strasse 3a, 37075 Göttingen, Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. Markus Zweckstetter
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Von-Siebold-Strasse 3a, 37075 Göttingen, Germany
Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, 37077 Göttingen, Germany
Department of Neurology, University Medical Center Göttingen, University of Göttingen, Waldweg 33, 37073 Göttingen, Germany
Search for more papers by this authorDr. Jin Hae Kim
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Von-Siebold-Strasse 3a, 37075 Göttingen, Germany
Search for more papers by this authorDr. Javier Oroz
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Von-Siebold-Strasse 3a, 37075 Göttingen, Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. Markus Zweckstetter
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Von-Siebold-Strasse 3a, 37075 Göttingen, Germany
Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, 37077 Göttingen, Germany
Department of Neurology, University Medical Center Göttingen, University of Göttingen, Waldweg 33, 37073 Göttingen, Germany
Search for more papers by this authorGraphical Abstract
Insights in solution: NMR spectroscopy reveals a unique, non-native structure of a monomeric transthyretin protein that carries the clinically important T119M mutation and thereby suggests a mechanism that contributes to protection from amyloid disease.
Abstract
Mutations in the protein transthyretin can cause as well as protect individuals from transthyretin amyloidosis, an incurable fatal inherited disease. Little is known, however, about the structural basis of pathogenic and clinically protective transthyretin mutants. Here we determined the solution structure of a transthyretin monomer that carries the clinically important T119M mutation. The structure displays a non-native arrangement that is distinct from all known structures of transthyretin and highlights the importance of high-resolution studies in solution for understanding molecular processes that lead to amyloid diseases.
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