Electron crystallography of three dimensional protein crystals
Georgieva, D.
Citation
Georgieva, D. (2008, December 11). Electron crystallography of three dimensional protein crystals. Retrieved from https://hdl.handle.net/1887/13354
Version: Corrected Publisher’s Version
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Electron Crystallography of Three Dimensional Protein Crystals
Dilyana Georgieva
Electron Crystallography of Three Dimensional Protein Crystals
PROEFSCHRIFT
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof. mr. P. F. van der Heiden, volgens besluit van het College voor Promoties,
te verdedigen op donderdag 11 december 2008 klokke 10.00 uur
door
Dilyana Georgieva
Geboren te Sofia, Bulgarije
in 1980
Promotiecommissie
Promotor: Prof. dr. J.P. Abrahams Overige leden: Prof. dr. J. Brouwer
Prof. dr. H. W. Zandbergen Prof. dr. M. Noteborn
Prof. dr. S. Hovmöler Dr. R. de Graaff Dr. N. Pannu
Dr. S. Nikolopoulus
Dr. M. Kuil
This thesis is part of the research program Stichting voor Fundamenteel Onderzoek der Materie (FOM), financially supported by Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO).
Contents
CHAPTER 1 INTRODUCTION... 1
1.1 OUTLINE... 1
1.2 STRUCTURAL ANALYSIS... 4
1.3 PROTEIN NUCLEATION AND CRYSTALLIZATION... 5
1.4 THE ROLE OF HETEROGENEOUS SUBSTRATES IN THE PROCESS OF PROTEIN NUCLEATION AND CRYSTALLIZATION... 9
1.5 PROTEIN NANO-CRYSTALLIZATION... 10
1.6 FLUORESCENCE MICROSCOPY... 14
1.7 ATOMIC FORCE MICROSCOPY... 16
1.8 TRANSMISSION ELECTRON MICROSCOPY... 16
REFERENCES... 23
CHAPTER 2 HETEROGENEOUS NUCLEATION OF 3D PROTEIN NANO- CRYSTALS... 25
ABSTRACT... 25
2.1 INTRODUCTION... 25
2.2 EXPERIMENTAL PROCEDURES... 27
2.3 RESULTS AND DISCUSSION... 30
2.4 CONCLUSIONS... 37
REFERENCES... 38
CHAPTER 3 PREPARING 3D PROTEIN NANO-CRYSTALS FOR ELECTRON DIFFRACTION STUDIES... 39
ABSTRACT... 39
3.1 INTRODUCTION... 39
3.2 EXPERIMENTAL PROCEDURES... 43
3.3 RESULTS AND DISCUSSION... 45
3.4 CONCLUSIONS... 50
REFERENCES... 52
CHAPTER 4 HIGH RESOLUTION ELECTRON DIFFRACTION OF 3D PROTEIN NANO-CRYSTALS: OPTIMIZING 3D DATA COLLECTION AND DATA ANALYSIS... 53
ABSTRACT... 53
4.1 INTRODUCTION... 54
4.2 EXPERIMENTAL PROCEDURES... 57
4.3 RESULTS AND DISCUSSION... 58
4.4 CONCLUSIONS... 77
REFERENCES... 80
CHAPTER 5 HIGH RESOLUTION ELECTRON DIFFRACTION OF PENICILLIN-TYPE NANO-CRYSTALS: 3D DATA COLLECTION AND DATA ANALYSIS... 81
ABSTRACT... 81
5.1 INTRODUCTION... 82
5.2 RESULTS AND DISCUSSION... 84
5.3 CONCLUSIONS... 100
REFERENCES... 101
CHAPTER 6 SUMMARY, CONCLUSIONS AND FUTURE PERSPECTIVES ... 103
NEDERLANDSE SAMENVATTING... 107
CURRICULUM VITAE ... 109
ACKNOWLEDGEMENTS ... 111
LIST OF PUBLICATIONS ... 113