Structural insights into the basis and evolution of interactions in multi-subunit protein assemblies. tryptophan synthase and titin FNIII-repeats

摘要

Cellular processes benefit from evolutionary shaping when optimized protein-protein interactions result in enhanced functionality. In fact, most cellular proteins are tightly embedded into biological networks that function following a modularity principle. Modularity, whether based on components as parts of stable protein complexes or as dynamic units that interact only transiently (as in signalling and metabolic cascades), facilitates the combinatorial generation of complexity in protein networks through the re-wiring of modules in addition to the diversification of individual proteins – thereby increasing the “evolvability” of the system. The mechanisms that drive the emergence and evolution of molecular recognition in protein networks remain unclear. It is difficult to justify such evolution on the basis of organismic advantage, since the latter might only be noticeable once full pathways and cascades have evolved. It is then likely that the evolution of protein-protein interactions is in the first instance driven by a molecular principle of local advantage to the protein system itself - for example, molecular stability. Unfortunately, it is difficult to gain insights into the evolution of protein-protein interactions since the pathways of evolutionary shaping normally let intermediates of evolution disappear. Subsequently, conclusions are more usually drawn from the comparison of proteins between different species and by mutagenesis probing. In the current study, we aim at gaining an insight into the evolutionary shaping of proteins surfaces for hetero-complex formation by studying two systems at an early stage of development: Tryptophan Synthase B2b (TrpB2b) from S. solfataricus and the modular interfaces of the poly-FNIII tandems in the muscle filament titin. In the case of TrpB2b, the evolution of inter-subunit communication is addressed in addition. Both structures have been elucidated using X-ray crystallography and a comparative analysis of their surfaces has been carried out. The architectural elements subjected to evolutionary pressure have been identified and conclusions on their relation to function and evolution have been drawn.ud