Title : Intrinsic Disorder in Transmembrane Proteins: Roles in Signaling and Topology Prediction
Abstract :
- Intrinsically disordered regions (IDRs) are peculiar stretches of amino acids that lack stable conformations in solution
- Intrinsic Disorder containing Proteins (IDP ) are defined by the presence of at least one large IDR and have been linked to multiple cellular processes including cell signaling, DNA binding and cancer
- Here we used computational analyses and publicly available databases to deepen insight into the prevalence and function of IDRs specifically in transmembrane proteins , which are somewhat neglected in most studies
- We found that 50% of transmembrane proteins have at least one IDR of 30 amino acids or more
- Interestingly, these domains preferentially localize to the cytoplasmic side especially of multi-pass transmembrane proteins , suggesting that disorder prediction could increase the confidence of topology prediction algorithms
- This was supported by the successful prediction of the topology of the uncharacterized multi-pass transmembrane protein TMEM117 , as confirmed experimentally
- Pathway analysis indicated that IDPs are enriched in cell projection and axons and appear to play an important role in cell adhesion, signaling and ion binding
- In addition, we found that IDP are enriched in phosphorylation sites , a crucial post translational modification in signal transduction, when compared to fully ordered proteins and to be implicated in more protein- protein interaction events
- Accordingly, IDPs were highly enriched in short protein binding regions called Molecular Recognition Features (MoRFs)
- Altogether our analyses strongly support the notion that the transmembrane IDPs act as hubs in cellular signal events