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Molecular basis of sequence-specific single-stranded DNA recognition by KH domains: solution structure of a complex between hnRNP K KH3 and single-stranded DNA.

Demetrios T Braddock·James L Baber·David Levens·G Marius Clore
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Abstract

To elucidate the basis of sequence-specific single-stranded (ss) DNA recognition by K homology (KH) domains, we have solved the solution structure of a complex between the KH3 domain of the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K) and a 10mer ssDNA. We show that hnRNP K KH3 specifically recognizes a tetrad of sequence 5'd-TCCC. The complex is stabilized by a dense network of methyl-oxygen hydrogen bonds involving the methyl groups of three isoleucine residues and the O2 and N3 atoms of the two central cytosine bases. Comparison with the recently solved structure of a specific protein-ssDNA complex involving the KH3 and KH4 domains of the far upstream element (FUSE) binding protein FBP suggests that the amino acid located five residues N-terminal of the invariant GXXG motif, which is characteristic of all KH domains, plays a crucial role in discrimination of the first two bases of the tetrad.

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Amino Acid MotifsAmino Acid SequenceBase SequenceCrystallography, X-RayDNA HelicasesDNA, Single-StrandedDNA-Binding ProteinsHeterogeneous-Nuclear Ribonucleoprotein KHeterogeneous-Nuclear RibonucleoproteinsHumansHydrogen BondingModels, MolecularMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularNucleic Acid ConformationProtein BindingProtein ConformationProtein Structure, TertiaryRNA-Binding ProteinsRibonucleoproteinsSequence AlignmentSequence Homology, Amino AcidSolutionsSubstrate SpecificityComparative StudyJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Demetrios T Braddock, James L Baber, David Levens, G Marius Clore. 2002-07-01. Molecular basis of sequence-specific single-stranded DNA recognition by KH domains: solution structure of a complex between hnRNP K KH3 and single-stranded DNA.. https://doi.org/10.1093/emboj%2Fcdf352

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