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Stability and crystal structures of His88 mutant human transthyretins
Author(s) -
Yokoyama Takeshi,
Hanawa Yuma,
Obita Takayuki,
Mizuguchi Mineyuki
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12704
Subject(s) - mutant , chemistry , biophysics , crystallography , biology , biochemistry , gene
Destabilization of human transthyretin (TTR) has been implicated in its misfolding and aggregation. A previous study on the neutron crystal structure of TTR suggested that a large hydrogen bond network around H88 which includes water molecules is significantly involved in the stability of wild‐type TTR (WT‐TTR). Here, we demonstrate that the H88R mutant associated with amyloid cardiomyopathy is substantially destabilized compared with WT‐TTR. In order to clarify the role of H88 and the hydrogen bond network in the stability of TTR, we determined the thermodynamic stability and the crystal structure of H88 mutants (H88A, H88F, H88Y, and H88S). Our results suggest that in some cases TTR is destabilized due to alterations in bound water molecules as well as structural changes in TTR itself.