Poster Presentation The 44th Lorne Conference on Protein Structure and Function 2019

Exploring three KH domains of hnRNPK in complex with single-stranded nucleic acids (#249)

Brian Le 1
  1. University of Western Australia, Perth, WESTERN AUSTRALIA, Australia

The heterogeneous nuclear ribonucleoprotein K (hnRNPK), found in both the nucleus and cytoplasm of mammalian cells, participates in multiple signalling pathways and processes involving nucleic acids. hnRNPK’s structure contains three hnRNPK homology (KH) domains KH1, KH2, and KH3 which appear to be pivotal to the binding of ssDNA and ssRNA. Earlier interaction work with C-rich sequences indicated that three KH domains of hnRNPK bind RNA in different ways. To address the precise role of each KH domain in RNA binding, full-length hnRNPK, KH1-KH2 tandem domain, and isolated KH1 domain were utilized along with a series of RNAs carrying two C4 motifs. My objective is to use microscale thermophoresis (MST) technique to explore the contribution of each KH domain in RNA binding. My MST result showed that when interacting with RNAs containing 2 C4 motifs, both KH1 domain and full-length hnRNPK produced multiple binding events, while KH1-KH2 domain exhibited weak binding to the RNAs compared to the full-length protein. These data revealed the difference in binding affinity between full-length hnRNPK, and KH1-KH2 domain to RNAs, suggesting a binding mechanism of hnRNPK to RNAs with KH1-KH2 performs as a tandem domain and KH3 as a separated binding domain.