Illustrative models of PI3K regulatory subunit dimers.
In each case, one monomer (named chain A) is shown in bright colours while the other (chain B) is in paler colours. The domains and regions of the proteins are labelled with a subscript to denote their chain. A key to the domain colours is shown in the schematics on the right of each model. Regions of unknown structure are indicated by dotted lines. (A) An N-terminal dimer model based on a combination of SAXS and cross-linking data [29]. Several models were consistent with the data but all have dimerisation interfaces between the SH3 domain of one chain and PR1 of the other chain, and between the cSH2 domains. We selected this model because a parallel orientation of the iSH2 coiled-coils was marginally favoured and there are interactions between the BH domains, which has been observed in multiple structures and shown by mutagenesis [28]. PR1 is shown as a space-filling representation. (B) A C-terminal dimer model based on the interaction between a phosphorylated tyrosine at the C-terminus of the iSH2 and the nSH2 domain of the other monomer. The phospho-Tyr is shown in a red space-filling representation. These dimers can be formed by two full-length regulatory subunits (p85–p85) or by the shorter isoforms (e.g. p85–p50/p55), as indicated in the schematic on the right.