2LRR

Solution structure of the R3H domain from human Smubp-2 in complex with 2'-deoxyguanosine-5'-monophosphate

Summary for 2LRR

• Entry DOI: 10.2210/pdb2lrr/pdb
• Related: 1msz
• NMR Information: BMRB: 18391
• Descriptor: DNA-binding protein SMUBP-2, 2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE (2 entities in total)
• Functional Keywords: dna binding protein, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P38935
• Total number of polymer chains: 1
• Total formula weight: 10054.07

Authors

Jaudzems, K.,Zhulenkovs, D.,Otting, G.,Liepinsh, E. (deposition date: 2012-04-12, release date: 2012-10-24, Last modification date: 2024-05-15)

Primary citation

Jaudzems, K.,Jia, X.,Yagi, H.,Zhulenkovs, D.,Graham, B.,Otting, G.,Liepinsh, E.
Structural Basis for 5'-End-Specific Recognition of Single-Stranded DNA by the R3H Domain from Human Smubp-2
J.Mol.Biol., 12:760-767, 2012

PubMed Abstract: The R3H domain is a conserved sequence motif in nucleic acid binding proteins. Previously, we reported the solution structure of the R3H domain and identified a putative nucleic acid binding site composed of three conserved basic residues [Liepinsh, E., Leonchiks, A., Sharipo, A., Guignard, L. & Otting, G. (2003). Solution structure of the R3H domain from human Sμbp-2. J. Mol. Biol.326, 217-223]. Here, we determine the binding affinities of mononucleotides and dinucleotides for the R3H domain from human Sμbp-2 (Sμbp2-R3H) and map their binding sites on the protein's surface. Although the binding affinities show up to 260-fold selectivity between different nucleotides, their binding sites and conformations seem very similar. Further, we report the NMR structure of the Sμbp2-R3H in complex with deoxyguanosine 5'-monophosphate (dGMP) mimicking the 5'-end of single-stranded DNA. Pseudocontact shifts from a paramagnetic lanthanide tag attached to residue 731 in the mutant A731C confirmed that binding of dGMP brings a loop of the protein into closer proximity. The structure provides the first structural insight into single-stranded nucleic acid recognition by the R3H domain and shows that the R3H domain specifically binds the phosphorylated 5'-end through electrostatic interactions with the two conserved arginines and stacking interactions with the highly conserved histidine.

PubMed: 22999958
DOI: 10.1016/j.jmb.2012.09.010

Experimental method

SOLUTION NMR