Approaches to Analyze Protein-Protein Interactions of Membrane Proteins

It can be estimated that most membrane proteins function in complexes (Fig. 1) (Daley 2008). Protein-protein interactions (PPIs) within these complexes can either be direct (primary interaction) or indirect (secondary interaction). Direct interactions occur either by homooligomerisation as determined for bacterial two-component systems (Gao and Stock 2009) (Fig. 1A) or by hetero-oligomerisation as shown for transport systems like ATP-binding cassette (ABC) transporters (Figs. 1B and 1C). Indirect interactions exist in large complexes as exemplified in energy producing systems such as the photosystem, bacterial surface appendages such as flagella, or secretion systems that even span two membrane systems in Gram-negative bacteria (Fig. 1D) (Jordan et al. 2001; Erhardt, Namba, and Hughes 2010). These high affinity, stable PPIs are important to form stable functional complexes (Jura et al. 2011). In addition, low affinity, transient PPIs are needed for proteins that regulate the activity of a stable complex and have been described for the interaction between e.g. ABC protein and inhibitory EIIaGlc (Blüschke et al. 2007; Blüschke, Volkmer-Engert, and Schneider 2006), substrate binding protein and ABC transporter (Locher, Lee, and Rees 2002) or accessory proteins in two-component systems (Heermann and Jung 2010; Buelow and Raivio 2010; Zhou et al. 2011).