The assembly of proteins into complexes is fundamental to nearly all biological signalling processes. Symmetry is a dominant feature of the structures of experimentally determined protein complexes, observed in the vast majority of homomers and many heteromers. However, some asymmetric structures exist, and asymmetry also often forms transiently, intractable to traditional structure determination methods. Here, we explore the role of protein complex symmetry and asymmetry in cellular signalling, focusing on receptors, transcription factors and transmembrane channels, among other signalling assemblies. We highlight a recurrent tendency for asymmetry to be crucial for signalling function, often being associated with activated states. We conclude with a discussion of how consideration of protein complex symmetry and asymmetry has significant potential implications and applications for pharmacology and human disease.
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Cover Image
Cover Image
An artistic model of the ‘molecular scissor’ ADAM10 (displayed in orange) at the cell surface, shown cleaving one of its substrates (green). ADAM10 is regulated by one of six TspanC8 tetraspanins (displayed in white or blue). The TspanC8s have distinct mechanisms of binding to ADAM10 and appear to dictate its substrate specificity. For more information, please see pages 719–730 in this issue of the Biochemical Society Transactions. Designer: Justyna Szyroka Artist: Eduardo Oliveira - Graphics Designer and Animator. Image kindly provided by Michael G Tomlinson.
Signalling assemblies: the odds of symmetry
Gábor Maksay, Joseph A. Marsh; Signalling assemblies: the odds of symmetry. Biochem Soc Trans 15 June 2017; 45 (3): 599–611. doi: https://doi.org/10.1042/BST20170009
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