Functional Analysis of Host-Pathogen Posttranslational Modification Crosstalk of Rab Proteins

Posttranslational modification (PTM) with functional groups is a universal mechanism for diversifying the activities of proteins. PTMs can affect many properties of proteins, such as localization, activity status, interaction networks, solubility, folding, turnover, or stability. This chapter describes the process of PTM identification using the adenylylation (i.e., the covalent transfer of an adenosine monophosphate (AMP)) of rat sarcoma related in brain (Rab) proteins by Legionella pneumophila enzymes as an example. It also deals with the development of PTM-specific antibodies from synthetic peptides. The chapter describes chemical and biochemical approaches to the preparative introduction of adenylylation into target proteins, to the analysis of the consequences of this PTM, and to the generation of reagents that allow global detection of adenylylated proteins. This account underlines the importance of chemical biology in the elucidation of PTMs.