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  Department of New Biology Theses Ph.D.

Dissecting The Mechanism of Structural Deformation in Transthyretin Amyloidosis

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dc.contributor.advisor 김진해 -
dc.contributor.author Jin-Beom Si -
dc.date.accessioned 2026-09-01T19:29:38Z -
dc.date.available 2026-09-01T19:29:38Z -
dc.date.issued 2026 -
dc.identifier.uri https://scholar.dgist.ac.kr/handle/20.500.11750/60728 -
dc.identifier.uri http://dgist.dcollection.net/common/orgView/200001021296 -
dc.description Transthyretin, amyloid, aggregation, neurodegenerative diseases -
dc.description.tableofcontents I. Introduction 1
1.1 Proteostasis and proteinopathies 1
1.2 Amyloid formation: mechanism, intermediates and pathological consequences 1
1.3 Molecular chaperones and small heat shock protein family 5
II. Structural and Thermodynamic Characterization of Pathogenic Dimeric Transthyretin Variants 7
2.1 Introduction 7
2.1.1 Structural characteristics and functional roles of transthyretin 7
2.1.2 The molecular basis of transthyretin amyloidosis （ATTR） 9
2.2 Materials and methods 12
2.2.1 Recombinant protein production and purification 12
2.2.2 Native-PAGE analysis 13
2.2.3 Analytical SEC and SEC-MALS 13
2.2.4 Circular dichroism （CD） spectroscopy 14
2.2.5 Intrinsic tryptophan fluorescence 14
2.2.6 Thioflavin T （ThT） and turbidity assays 14
2.2.7 [1H-15N] TROSY-HSQC NMR spectroscopy 15
2.2.8 Small-Angle X-ray scattering （SAXS） 15
2.3 Results and discussion 17
2.3.1 Distinct structural characteristics of TTR dimeric species 17
2.3.2 Discrete Biochemical properties of TTR dimers 22
2.3.3 Partially Unfolded or Flexible States of TTR Dimers 25
2.3.4 Conclusion 29
III. HSPB5 Arrests Transthyretin Aggregation by Targeting Early-Stage Misfolded Intermediates 31
3.1 Introduction 31
3.2 Materials and methods 34
3.2.1 Protein expression and purification 34
3.2.2 NMR spectroscopy 34
3.2.3 Turbidity assay and time-of-addition experiments 35
3.2.4 Transmission electron microscopy （TEM） 35
3.2.5 Analytical size-exclusion chromatography and SDS-PAGE 36
3.2.6 Mass photometry 36
3.2.7 Small-Angle X-ray scattering （SAXS） 37
3.3 Results and discussion 38
3.3.1 Conformation selective recognition of destabilized TTR by HSPB5 and its isolated ACD 38
3.3.2 The oligomeric architecture of HSPB5 is required for chaperone activity against TTR aggregation 41
3.3.3 Client engagement drives structural expansion and dynamic oligomeric remodeling of HSPB5 46
3.3.4 HSPB5 selectively targets soluble early-stage aggregation intermediates 50
3.3.5 Conclusions 54
References 58
국문 요약문 65		 -
dc.format.extent 66 -
dc.language eng -
dc.publisher DGIST -
dc.title Dissecting The Mechanism of Structural Deformation in Transthyretin Amyloidosis -
dc.title.alternative 트렌시스레틴 아밀로이드증에서 나타나는 구조적 변형의 기전 규명 -
dc.type Thesis -
dc.identifier.doi 10.22677/THESIS.200001021296 -
dc.description.degree Doctor -
dc.contributor.department Department of New Biology -
dc.contributor.coadvisor Jong-Chan Lee -
dc.date.awarded 2026-08-01 -
dc.publisher.location Daegu -
dc.description.database dCollection -
dc.citation XT.ND 시78 202608 -
dc.date.accepted 2026-07-21 -
dc.contributor.alternativeDepartment 뉴바이올로지학과 -
dc.subject.keyword Transthyretin, amyloid, aggregation, neurodegenerative diseases -
dc.contributor.affiliatedAuthor Jin-Beom Si -
dc.contributor.affiliatedAuthor Jin-Hae Kim -
dc.contributor.affiliatedAuthor Jong-Chan Lee -
dc.contributor.alternativeName 시진범 -
dc.contributor.alternativeName Jin-Hae Kim -
dc.contributor.alternativeName 이종찬 -
dc.rights.embargoReleaseDate 2031-02-28 -
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