Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain: a gamma-secretase substrate
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130712-1140433-0-0 Inhaltsverzeichnis |
| Physical Description: | 6, III, 151 S. graph. Darst. |
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MARC
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| 100 | 1 | |a Pester, Oxana |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain |b a gamma-secretase substrate |c Oxana Pester |
| 264 | 1 | |c 2013 | |
| 300 | |a 6, III, 151 S. |b graph. Darst. | ||
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| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |a München, Techn. Univ., Diss., 2013 | ||
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Record in the Search Index
| _version_ | 1804150742862266368 |
|---|---|
| adam_text | IMAGE 1
CONTENTS
ABSTRACT 1
ZUSAMMENFASSUNG 3
1 INTRODUCTION 5
1.1 STRUCTURAL PROPERTIES OF TRANSMEMBRANE DOMAINS 6
1.1.1 CHARACTERISTICS OF TRANSMEMBRANE DOMAINS 6
1.1.2 THE PEPTIDE BOND AND THE HYDROGEN BOND 7
1.1.3 SECONDARY STRUCTURE OF TRANSMEMBRANE DOMAINS 10
1.1.4 CONFORMATIONAL STABILITY AND DYNAMICS OF TRANSMEMBRANE HELICES 11
1.2 MEASURING THE STRUCTURAL PROPERTIES OF TM HELICES 16
1.2.1 CIRCULAR DICHROISM 16
1.2.2 PROBING HELIX DYNAMICS WITH HYDROGEN DEUTERIUM EXCHANGE 18
1.3 INTRAMEMBRANE PROTEOLYSIS IN ALZHEIMER S DISEASE 23
1.3.1 PRINCIPLES OF INTRAMEMBRANE PROTEOLYSIS 23
1.3.2 THE ETIOLOGY OF ALZHEIMER S DISEASE 24
1.3.3 ASSEMBLY, STRUCTURE AND FUNCTION OF THE 7 -SECRETASE 26
1.3.4 THE AMYLOID PRECURSOR PROTEIN 29
1.3.5 GENERATION OF A/5 PEPTIDES BY 7 -SECRETASE 31
1.3.6 SUBSTRATE SPECIFICITY OF 7 -SECRETASE 33
2 MOTIVATION AND AIM OF THESIS 35
3 MATERIALS AND METHODS 37
3.1 MATERIALS 37
3.1.1 CHEMICALS AND REAGENTS 37
3.1.2 INSTRUMENTS AND ACCESSORIES 37
3.1.3 SOFTWARE 38
3.1.4 PEPTIDES 39
3.1.5 LIPIDS 40
3.2 METHODS 41
3.2.1 PEPTIDE SOLUTIONS 41
3.2.2 PREPARATION OF SMALL UNILAMELLAR VESICLES (SUVS) 41
HTTP://D-NB.INFO/1042847533
IMAGE 2
II CONTENTS
3.2.3 DETERMINATION OF PEPTIDE/ LIPID RATIO OF SUVS 42
. 3.2.4 CIRCULAR DICHROISM 43
3.2.5 DEUTERIUM/HYDROGEN EXCHANGE REACTIONS 44
3.2.6 KINETIC ANALYSIS OF ISOTOPE EXCHANGE REACTIONS 47
3.2.7 MASS SPECTROMETRY ACQUISITION 49
3.2.8 SELECTION OF TRANSMEMBRANE DOMAINS WITH SIMILARITIES TO THE
AVERAGE AMINO ACID DISTRIBUTION 50
4 RESULTS 53
4.1 DESIGN OF MODEL PEPTIDES 53
4.2 STRUCTURAL PROPERTIES OF THE APP TRANSMEMBRANE DOMAIN 55
4.2.1 PRIMARY AND SECONDARY STRUCTURE OF THE APP TRANSMEMBRANE
DOMAIN 55
4.2.2 D/H EXCHANGE AND BACKBONE DYNAMICS OF THE APP TRANSMEM
BRANE DOMAIN 58
4.2.3 D/H EXCHANGE AND BACKBONE DYNAMICS OF THE APP TRANSMEM
BRANE DOMAIN IN PRESENCE OF NSAIDS 62
4.3 IMPACT OF THREONINE BACKBONDING ON STRUCTURAL PROPERTIES OF APP TMD
64
4.3.1 SECONDARY STRUCTURE OF APP TMD THREONINE MUTANTS 64
4.3.2 D/H EXCHANGE AND BACKBONE DYNAMICS OF APP TMD THREONINE
MUTANTS 65
4.4 STRUCTURAL PROPERTIES OF HYBRID APP-TMD-PEPTIDES . 69
4.4.1 LIPOSOME INTEGRATION AND SECONDARY STRUCTURE OF HYBRID
APPTMD-PEPTIDES 69
4.4.2 D/H EXCHANGE AND BACKBONE DYNAMICS OF HYBRID APP-TMDPEPTIDES 72
4.5 STRUCTURAL COMPARISON OF APP-TMD AND LV PEPTIDES REPRESENTING
NON-APP-TMDS 77
4.6 STRUCTURAL PROPERTIES OF NATURAL NON-APP-TMDS 80
4.6.1 COMPOSITION SIMILARITY ANALYSIS AND SELECTION OF TMDS OF BITOPIC
MEMBRANE PROTEINS 80
4.6.2 SECONDARY STRUCTURE OF SELECTED NATURAL TMDS COMPARED TO THE
APP TMD 83
4.6.3 COMPARISON OF D/H EXCHANGE AND BACKBONE DYNAMICS OF NATURAL
TMDS AND THE APP-TMD 85
4.6.4 COMPARISON OF D/H EXCHANGE AND BACKBONE DYNAMICS OF NATURAL
TMDS AND THE APP TMD CLEAVAGE REGION 87
4.6.5 COMPARISON OF BACKBONE DYNAMICS OF KTMDS WITH THR APP
TMD MUTANTS 90
IMAGE 3
CONTENTS III
5 DISCUSSION 93
5.1 MAPPING THE CONFORMATIONAL PROPERTIES OF THE APP TRANSMEMBRANE
DOMAIN 93
5.2 HOW DOES APP TMD BACKBONE DYNAMICS INFLUENCE 7 -SECRETASE MEDI
ATED CLEAVAGE 97
5.3 NSAIDS DO NOT IMPAIR BACKBONE DYNAMICS OF LYS-FLANKED APP TMD
IN 80% (V/V) TFE 100
5.4 THR BACKBONDING IN THE APP TMD INCREASES HELIX STABILITY 101
5.5 ANALYSIS OF APP TMD FRAGMENTS GIVES SITE-RESOLVED INFORMATION ON
DYNAMICS 104
5.6 COMPARING BACKBONE DYNAMICS OF THE APP TMD WITH THAT OF NONAPP-TMDS
107
5.6.1 HELIX DYNAMICS OF ARTIFICIAL NON-APP-TMDS 108
5.6.2 HELIX DYNAMICS OF NATURAL NON-APP-TMDS 108
5.7 CONCLUSIONS AND OUTLOOK 110
LIST OF ABBREVIATIONS 113
LIST OF FIGURES 115
LIST OF TABLES 117
BIBLIOGRAPHY 119
A APPENDIX 145
PUBLICATION LIST 149
|
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| discipline | Biologie Chemie Medizin |
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| institution | BVB |
| language | English |
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| physical | 6, III, 151 S. graph. Darst. |
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| publishDate | 2013 |
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| spelling | Pester, Oxana Verfasser aut Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate Oxana Pester 2013 6, III, 151 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Techn. Univ., Diss., 2013 Mit einer Zssfassung in dt. Sprache (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:91-diss-20130712-1140433-0-0 http://mediatum.ub.tum.de/node?id=1140433 Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130712-1140433-0-0 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026248390&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Pester, Oxana Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate |
| subject_GND | (DE-588)4113937-9 |
| title | Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate |
| title_auth | Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate |
| title_exact_search | Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate |
| title_full | Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate Oxana Pester |
| title_fullStr | Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate Oxana Pester |
| title_full_unstemmed | Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain a gamma-secretase substrate Oxana Pester |
| title_short | Helix backbone dynamics of the Alzheimer amyloid precursor protein transmembrane domain |
| title_sort | helix backbone dynamics of the alzheimer amyloid precursor protein transmembrane domain a gamma secretase substrate |
| title_sub | a gamma-secretase substrate |
| topic_facet | Hochschulschrift |
| url | http://mediatum.ub.tum.de/node?id=1140433 https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130712-1140433-0-0 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026248390&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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