X-Ray crystallographic and nmr studies of protein-Protein and protein-Nucleic acid interactions involving the kh domains from human poly(c)-Binding protein-2.
Poly(C)-binding proteins (PCBPs) are KH (hnRNP K homology) domain-containing
proteins that recognize poly(C) DNA and RNA sequences in mammalian cells.
Binding poly(C) sequences via the KH domains is critical for PCBP functions. To
reveal the mechanisms of KH domain-D/RNA recognition and its functional
importance, we have determined the crystal structures of PCBP2 KH1 domain in
complex with a 12-nucleotide DNA corresponding to two repeats of the human
C-rich strand telomeric DNA and its RNA equivalent. The crystal structures
reveal molecular details for not only KH1-DNA/RNA interaction but also
protein-protein interaction between two KH1 domains. NMR studies on a protein
construct containing two KH domains (KH1 + KH2) of PCBP2 indicate that KH1
interacts with KH2 in a way similar to the KH1-KH1 interaction. The crystal
structures and NMR data suggest possible ways by which binding certain nucleic
acid targets containing tandem poly(C) motifs may induce structural
rearrangement of the KH domains in PCBPs; such structural rearrangement may be
crucial for some PCBP functions.
