JKMRS Volume 24, No 3, pp 91, NMR-based structural characteriz... | |
---|---|
2020년 09월 20일 / 조회수: 476 | |
NMR-based structural characterization of
transthyretin in its aggregation-prone state 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
|
|
첨부파일 | 05-JKMRS-JH_Kim.pdf |