|JKMRS Volume 24, No 3, pp 91, NMR-based structural characteriz...|
|2020년 09월 20일 / 조회수: 145|
Bokyung Kim and Jin Hae Kim*
Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea
Received Sep 18, 2020; Revised Sep 19, 2020; Accepted Sep 19, 2020
Abstract Transthyretin (TTR) is an abundant protein in blood plasma and cerebrospinal fluid (CSF), working as a homo-tetrameric complex to transport thyroxine (T4) and a holo-retinol binding protein. TTR is well-known for its amyloidogenic property; several types of systemic amyloidosis diseases are caused by aggregation of either wild-type TTR or its variants, for which more than 100 mutations were reported to increase the amyloidogenicity of TTR. The rate-limiting step of TTR aggregation is the dissociation of a monomeric subunit from a tetrameric complex. A wide range of biochemical and biophysical techniques have been employed to elucidate the TTR aggregation processes, among which nuclear magnetic resonance (NMR) spectroscopy contributed much to characterize the structural and functional features of TTR during its aggregation processes. The present review focuses on discussing the recent advances of our understanding to the amyloidosis mechanism of TTR and to the structural features of its monomeric aggregation-prone state in solution. We expect that the present review provides novel insights to appreciate the molecular basis of TTR amyloidosis and to develop novel therapeutic strategies to treat diverse TTR-related diseases.
Keywords transthyretin, transthyretin amyloidosis, amyloid, protein aggregation, NMR spectroscopy