Evolution and Dynamics of Protein Complexes: I

A lecture by Dr Sarah Teichmann of the MRC Laboratory of Molecular Biology, Cambridge, UK at the Institute of Structural and Molecular Biology Symposium, 21 June 2012

The ISMB is a joint institute between Birkbeck and UCL which aims to promote close links and a creative and inspiring interdisciplinary working environment with members drawn from chemistry, biology and structural molecular biology departments.  Every two years they hold a symposium to showcase the work of outstanding researchers from across the field and this year I was fortunate to attend. 

 

Dr Sarah Teichman is investigating the principles which govern protein-protein and protein-DNA interactions using a combination of computational biology methods and “wet” lab-based experiments.   In this lecture, she outlined some recent work on the formation of protein complexes, a topic which is covered from a variety of angles within the Principles of Protein Structure course, notably in Section 7, quaternary structure, and Section 10, protein interactions and function.

The first question raised in the lecture was how cellular proteins find their partner proteins within the crowded cellular environment.  The image below, created by Adrian Elcock’s group at the University of Iowa, is taken from a virtual E. coli cell’s cytoplasm and beautifully illustrates the difficulty of that mission.

Still from a Brownian Dynamics simulation of monomeric and complexed proteins in a virtual E. coli cell using known structures and concentrations by McGuffee, S.R., Elcock, A.H. (2010) Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm.  PLoS Comput. Biol. 6(3):e1000694

This leads to the questions of the mechanisms of protein assembly, whether these mechanisms are a driver for evolution and, crucially, whether proteins assemble along evolutionarily conserved processes which, when understood, would allow the prediction of interaction pathways.

A great deal of data is now available about the cellular protein interaction networks, or interactomes, of various species.  The complexity of this can be gauged from this image of the yeast interactome produced by (Yu, H. et al. (2008)), where each gene product is represented as a black dot and relationships are shown in red.

 

An image of the yeast interactome adapted from Yu, H. et al. (2008) High-quality binary protein interaction map of the yeast interactome network.  Science 322 (5898): 104-10

 Because of the data requirements of the images I have had to submit the second part of the piece as a separate post.....