Amino acid substitutions in protein binding [Elektronische Ressource] : a study for peptides and antibodies / von Armin A. Weiser

Amino acid substitutions in protein binding:A study for peptides and antibodiesDISSERTATIONzur Erlangung des akademischen Gradesdoctor rerum naturalium(Dr. rer. nat.)im Fach Biologieeingereicht an derMathematisch-Naturwissenschaftlichen Fakultät IHumboldt-Universität zu BerlinvonHerrn Dipl.-Math. Armin A. Weisergeboren am 11.12.1969 in Bad HersfeldPräsident der Humboldt-Universität zu Berlin:Prof. Dr. Christoph MarkschiesDekan der Mathematisch-Naturwissenschaftlichen Fakultät I:Prof. Dr. Lutz-Helmut SchönGutachter:1. Dr. Michal Or-Guil2. Prof. Cornelius Frömmel3. Prof. Sepp HochreiterTag der mündlichen Prüfung: 29. Juli 2009AbstractA central task of the evolutionary process is the alteration of amino acidsequences, such as the substitution of one amino acid by another. Not onlydo these amino acid changes occur gradually over large time scales and resultin the variety of life surrounding us, but they also happen daily within an or-ganism. Suchalterationstakeplacerapidlyforthepurposesofdefense, whichin higher vertebrates, is managed by the humoral immune system. For aneffective immune response, antibodies are subjected to a micro-evolutionaryprocess that includes multiple rounds of diversification by somatic hypermu-tation resulting in increased binding affinity to a particular pathogen. Incontrast to recent advances in revealing the molecular mechanism of somatichypermutation, the fundamentals of the selection process are still poorlyunderstood.