The mechanism of peptide exchange by MHC class II molecules:
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| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | Volltext Inhaltsverzeichnis |
| Item Description: | Nebentitel: Der Austauschmechanismus von Peptiden bei MHC-Klasse-II-Molekülen |
| Physical Description: | XIV, 91 Bl. Ill., graph. Darst. |
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MARC
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| 100 | 1 | |a Schulze, Monika-Sarah |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a The mechanism of peptide exchange by MHC class II molecules |c by Monika-Sarah Schulze |
| 246 | 1 | 3 | |a Der Austauschmechanismus von Peptiden bei MHC-Klasse-II-Molekülen |
| 264 | 1 | |c 2012 | |
| 300 | |a XIV, 91 Bl. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Nebentitel: Der Austauschmechanismus von Peptiden bei MHC-Klasse-II-Molekülen | ||
| 502 | |a Berlin, Freie Univ., Diss., 2012 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 776 | 0 | 8 | |i Erscheint auch als |n Online-Ausgabe |o urn:nbn:de:kobv:188-fudissthesis000000037593-2 |
| 856 | 4 | 1 | |u http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000037593 |z kostenfrei |3 Volltext |
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| 912 | |a ebook | ||
| 999 | |a oai:aleph.bib-bvb.de:BVB01-025011021 | ||
Record in the Search Index
| _version_ | 1804149180901359616 |
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| adam_text | IMAGE 1
TABLE O F CONTENTS
XII
TABLE O F CONTENTS
GUTACHTER II
DECLARATION III
ACKNOWLEDGMENT IV
SUMMARY V
ZUSAMMENFASSUNG VII
LIST O F PUBLICATIONS X
LIST O F ABBREVIATIONS X I
TABLE O F CONTENTS XII
1 INTRODUCTION 1
1.1 THE MAJOR HISTOCOMPATIBILITY COMPLEX 1
1.2 MHC CLASS II DEPENDENT PATHWAY O F ANTIGEN PRESENTATION 2
1.3 STRUCTURE AND FUNCTION O F MHC CLASS II/PEPTIDE COMPLEX AND
COMPARISON
WITH MHC CLASS I/PEPTIDE COMPLEX 5
1.4 THE ROLE O F HLA-DM IN THE MHC CLASS II PRESENTATION PATHWAY AND
COMPARISON TO THE PEPTIDE LOADING COMPLEX O F MHC CLASS I MOLECULES 9
1.5 STRUCTURE O F HLA-DM AND LATERAL INTERACTION WITH HLA-DR 11
1.6 PROPOSED MECHANISMS FOR HLA-DM-CATALYZED PEPTIDE EXCHANGE 14
1.7 HLA-DO: A NEGATIVE REGULATOR O F HLA-DM 16
1.8 MHC LOADING ENHANCERS 17
1.9 SCOPES AND OBJECTIVES O F THIS STUDY 21
2 CHAPTER I: INVESTIGATING ENHANCED PEPTIDE EXCHANGE O F M H C CLASS I I
MOLECULES
BY THE SMALL MOLECULE CATALYST J10 22
2.1 INTRODUCTION 22
2.2 MATERIALS AND METHODS 24
2.2.1 PREPARATION AND CRYSTALLIZATION O F H L A - D R 2 / M B P IN THE
PRESENCE O F J10-1 AND J 1 0 - 1 2 .
2 4
2.2.2 PREPARATION O F ISOTOPE LABELED M B P PEPTIDE 2 5
2.2.3 PREPARATION O F HLA-DR2/PEPTIDE COMPLEXES 2 6
2.2.4 N M R EXPERIMENTS 2 7
2.3 RESULTS AND DISCUSSION 28
HTTP://D-NB.INFO/102519215X
IMAGE 2
TABLE O F CONTENTS
XIII
2.3.1 PREPARING AND CRYSTALLIZING H L A - D R 2 / M B P IN THE PRESENCE
O F J10-1 OR J10-12 2 8
2.3.2 PREPARING AND CHARACTERIZING 15N-LABELED M B P PEPTIDE 29
2.3.3 PREPARING THE COMPLEX O F H L A - D R 2 AND L5N-LABELED M B P
PEPTIDE 31
2.3.4 MEASURING H - ^ N H S Q C SPECTRA O F 15N-LABELED M B P PEPTIDE
FREE IN SOLUTION AND IN
COMPLEX WITH H L A - D R 2 31
2.3.5 DEUTERATING M B P PEPTIDE TO IMPROVE SIGNAL INTENSITY O F THE H S
Q C SPECTRUM O F ISOTOPE
LABELED M B P PEPTIDE IN COMPLEX WITH H L A - D R 2 3 5
2.3.6 MEASURING AND COMPARING H S Q C SPECTRA O F HLA-DR2/
I: N,13C,2H-MBP BEFORE AND
AFTER ADDITION O F J10-1 36
2.3.7 PERFORMING H N C A AND L 5 N - N O E S Y EXPERIMENTS O F H L A - D
R 2 / I 5 N , I 3 C , 2 H - M B P T O
DETERMINE RESONANCE ASSIGNMENTS 39
2.3.8 MEASURING 19F-NMR SPECTRA O F J10-11 IN THE PRESENCE O F H L A - D
R 2 / M B P AND H L A DR2/CL1P 4 0
2.4 CONCLUSION 42
3 CHAPTER II: STRUCTURAL EFFECTS O F DESTABILIZING PEPTIDE-MHC I I
INTERACTIONS AND
IMPLICATIONS F O R THE PEPTIDE EXCHANGE MECHANISM O F HLA-DM. 46
3.1 INTRODUCTION 46
3.2 MATERIALS AND METHODS 47
3.2.1 PREPARATION O F BIOTINYLATED H L A - D M AND H L A - D M MUTANT 4
7
3.2.2 PREPARATION O F H L A - D M USED FOR CRYSTALLIZATION 4 8
3.2.3 PREPARATION O F COVALENTLY LINKED H L A - D R L / P E P T I D E
COMPLEXES AND O F HLA-DR1
MUTANT 4 8
3.2.4 PREPARATION O F H L A - D M WITH AN N-TERMINALLY TRUNCATED A CHAIN
4 9
3.2.5 SURFACE PLASMON RESONANCE EXPERIMENTS 4 9
3.2.6 PROTEIN CRYSTALLIZATION, COLLECTION O F DIFFRACTION DATA AND
STRUCTURE SOLVING 50
3.2.7 ELUTING COVALENTLY LINKED PEPTIDE FROM HLA-DR1 51
3.2.8 MASS SPECTROMETRY 51
3.3 RESULTS AND DISCUSSION 51
3.3.1 PREPARING H L A - D M AND HLA-DR1 CARRYING A TRUNCATED H A
PEPTIDE, BOTH USED FOR
CRYSTALLIZATION EXPERIMENTS 51
3.3.2 MEASURING PH-DEPENDENT AFFINITY O F H L A - D M TO HLA-DR1
CARRYING A N N-TERMINALLY
TRUNCATED H A PEPTIDE USING SURFACE PLASMON RESONANCE 53
3.3.3 CRYSTALLIZING HLA-DR1 CARRYING A TRUNCATED H A PEPTIDE, IN THE
PRESENCE O F H L A - D M
AND ALONE 55
3.3.4 SOLVING THE STRUCTURE O F HLA-DR1 CARRYING AN N-TERMINALLY
TRUNCATED H A PEPTIDE.... 5 6
3.3.5 STRUCTURE O F HLA-DR1 CARRYING A N N-TERMINALLY TRUNCATED H A
PEPTIDE 57
3.3.6 ELUTING N-TERMINALLY TRUNCATED H A PEPTIDE FROM HLA-DR1 PROTEIN
USED FOR
CRYSTALLIZATION AND ANALYZING B Y MASS SPECTROMETRY 65
IMAGE 3
TABLE O F CONTENTS XIV
3.3.7 MEASURING H L A - D R BINDING TO N-TERMINALLY TRUNCATED H L A - D
M USING SURFACE
PLASMON RESONANCE 67
3.3.8 MEASURING H L A - D M BINDING TO HLA-DR1 CARRYING A N H A PEPTIDE
VARIANT WITH A
VALINE AT PI POSITION AND TWO N-TERMINAL PEPTIDE RESIDUES ABSENT 6 8
3.3.9 MEASURING H L A - D M BINDING TO HLA-DR1 MUTANT (VALL385ASP) USING
SURFACE PLASMON
RESONANCE 69
3.4 CONCLUSION 71
4 CHAPTER III: INVESTIGATING HLA-DM BINDING TO HIGH-AFFINITY M H C
IL/PEPTIDE
COMPLEXES 74
4.1 INTRODUCTION 74
4.2 MATERIALS AND METHODS 75
4.2.1 PREPARATION O F HLA-DR/PEPTIDE COMPLEXES 75
4.2.2 SURFACE PLASMON RESONANCE EXPERIMENTS 7 6
4.2.3 FLUORESCENCE POLARIZATION EXPERIMENTS 7 6
4.3 RESULTS AND DISCUSSION 76
4.3.1 PREPARING THE HIGH-AFFINITY COMPLEXES H L A - D R 2 / M B P AND H
L A - D R 1 / H A 7 6
4.3.2 MEASURING H L A - D M BINDING TO H L A - D R 2 / M B P AND H L A -
D R 1 / H A USING SURFACE
PLASMON RESONANCE 77
4.3.3 COMPARING H L A - D M BINDING DETECTED B Y SURFACE PLASMON
RESONANCE WITH H L A - D M
CATALYSIS MEASURED BY FLUORESCENCE POLARIZATION 7 8
4.4 CONCLUSION 79
5 FINAL DISCUSSION AND OUTLOOK. 80
6 REFERENCES 84
|
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| author | Schulze, Monika-Sarah |
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| dewey-ones | 572 - Biochemistry |
| dewey-raw | 572 |
| dewey-search | 572 |
| dewey-sort | 3572 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| format | Thesis Book |
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| indexdate | 2024-07-10T00:18:56Z |
| institution | BVB |
| language | English |
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| physical | XIV, 91 Bl. Ill., graph. Darst. |
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| spelling | Schulze, Monika-Sarah Verfasser aut The mechanism of peptide exchange by MHC class II molecules by Monika-Sarah Schulze Der Austauschmechanismus von Peptiden bei MHC-Klasse-II-Molekülen 2012 XIV, 91 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Nebentitel: Der Austauschmechanismus von Peptiden bei MHC-Klasse-II-Molekülen Berlin, Freie Univ., Diss., 2012 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:kobv:188-fudissthesis000000037593-2 http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000037593 kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025011021&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Schulze, Monika-Sarah The mechanism of peptide exchange by MHC class II molecules |
| subject_GND | (DE-588)4113937-9 |
| title | The mechanism of peptide exchange by MHC class II molecules |
| title_alt | Der Austauschmechanismus von Peptiden bei MHC-Klasse-II-Molekülen |
| title_auth | The mechanism of peptide exchange by MHC class II molecules |
| title_exact_search | The mechanism of peptide exchange by MHC class II molecules |
| title_full | The mechanism of peptide exchange by MHC class II molecules by Monika-Sarah Schulze |
| title_fullStr | The mechanism of peptide exchange by MHC class II molecules by Monika-Sarah Schulze |
| title_full_unstemmed | The mechanism of peptide exchange by MHC class II molecules by Monika-Sarah Schulze |
| title_short | The mechanism of peptide exchange by MHC class II molecules |
| title_sort | the mechanism of peptide exchange by mhc class ii molecules |
| topic_facet | Hochschulschrift |
| url | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000037593 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025011021&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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