Analysis of electric moments of RNA-binding proteins: implications for mechanism and prediction

Ahmad, Shandar; Sarai, Akinori
January 2011
BMC Structural Biology;2011, Vol. 11 Issue 1, p8
Academic Journal
Background: Protein-RNA interactions play important role in many biological processes such as gene regulation, replication, protein synthesis and virus assembly. Although many structures of various types of protein-RNA complexes have been determined, the mechanism of protein-RNA recognition remains elusive. We have earlier shown that the simplest electrostatic properties viz. charge, dipole and quadrupole moments, calculated from backbone atomic coordinates of proteins are biased relative to other proteins, and these quantities can be used to identify DNA-binding proteins. Closely related, RNA-binding proteins are investigated in this study. In particular, discrimination between various types of RNA-binding proteins, evolutionary conservation of these bulk electrostatic features and effect of conformational changes by complex formation are investigated. Basic binding mechanism of a putative RNA-binding protein (HI1333 from Haemophilus influenza) is suggested as a potential application of this study. Results: We found that similar to DNA-binding proteins (DBPs), RNA-binding proteins (RBPs) also show significantly higher values of electric moments. However, higher moments in RBPs are found to strongly depend on their functional class: proteins binding to ribosomal RNA (rRNA) constitute the only class with all three of the properties (charge, dipole and quadrupole moments) being higher than control proteins. Neural networks were trained using leave-one-out cross-validation to predict RBPs from control data as well as pair-wise classification capacity between proteins binding to various RNA types. RBPs and control proteins reached up to 78% accuracy measured by the area under the ROC curve. Proteins binding to rRNA are found to be best distinguished (AUC = 79%). Changes in dipole and quadrupole moments between unbound and bound structures were small and these properties are found to be robust under complex formation. Conclusions: Bulk electric moments of proteins considered here provide insights into target recognition by RNA-binding proteins, as well as ability to recognize one type of RBP from others. These results help in understanding the mechanism of protein-RNA recognition, and identifying RNA-binding proteins.


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