Structural characteristics
Two structural models were obtained with RaptorX and Phyre2 (see Models). We will examine and compare structural features of these models. Jmol [1] has been used to analyse three dimensional structures.
Pleckstrin-homology (PH) domain
Both models predict a Pleckstrin homology-like domain at the N-terminus.
The model provided by RaptorX features two perpendicular, antiparallel β-sheets consisting of 3 and 4 strands, forming a β-barrel. An amphiphatic α-helix forms the base of the β-barrel.
This structure is typical of a PH-like domain [2]. In addition, there is a short α-helical segment joining the last and first strand of the β-sheets.
Phyre2 predicted a slightly different structure. A distorted β-sandwich consists of two β-sheets of 3 strands each. An amphiphatic α-helix is also present, though shorter. There are two short α-helical segments, part of an extended loop connecting the last and first strand of the β-sheets (RaptorX predicts a β-strand there). There are two antiparallel β-strands N-terminus to the PH domain.
Disordered regions
A significant part of the structure was predicted as disordered (RaptorX predicts 87% , Phyre2 predicts 39%). Disordered regions have no defined structure and consist mostly of hydrophilic amino-acids. The resulting flexibility allows flexibility in the interactions with its binding partners.
Although both models predict mainly α-helical structure N-terminal to the PH domain, there are significant differences in the models. Note that Phyre2 predicted only 27% of the structure while RaptorX predicted 48%.Phyre2 predicts a α-helix N-terminal to the PH domain.
References
1. Jmol: an open-source Java viewer for chemical structures in 3D.
2. Scheffzek, K., Welti, S. (2012) Pleckstrin homology (PH) like domains – versatile modules in protein–protein interaction platforms. FEBS Letters 586(17):2662–2673
Other features
This region is predicted as a disordered by RaptorX. Moreover, two β-helical regions (in green) are predicted by RaptorX.