2KMU

RecQL4 Amino-terminal Domain

Summary for 2KMU

• Entry DOI: 10.2210/pdb2kmu/pdb
• NMR Information: BMRB: 16544
• Descriptor: ATP-dependent DNA helicase Q4 (1 entity in total)
• Functional Keywords: recql4, helicase, dna-replication, homeodomain-like, atp-binding, cataract, craniosynostosis, disease mutation, dwarfism, hydrolase, nucleotide-binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 6850.65

Authors

Ohlenschlager, O.,Gorlach, M.,Pospiech, H. (deposition date: 2009-08-05, release date: 2010-07-07, Last modification date: 2024-05-15)

Primary citation

Ohlenschlager, O.,Kuhnert, A.,Schneider, A.,Haumann, S.,Bellstedt, P.,Keller, H.,Saluz, H.P.,Hortschansky, P.,Hanel, F.,Grosse, F.,Gorlach, M.,Pospiech, H.
The N-terminus of the human RecQL4 helicase is a homeodomain-like DNA interaction motif
Nucleic Acids Res., 40:8309-8324, 2012

PubMed Abstract: The RecQL4 helicase is involved in the maintenance of genome integrity and DNA replication. Mutations in the human RecQL4 gene cause the Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. Mouse models and experiments in human and Xenopus have proven the N-terminal part of RecQL4 to be vital for cell growth. We have identified the first 54 amino acids of RecQL4 (RecQL4_N54) as the minimum interaction region with human TopBP1. The solution structure of RecQL4_N54 was determined by heteronuclear liquid-state nuclear magnetic resonance (NMR) spectroscopy (PDB 2KMU; backbone root-mean-square deviation 0.73 Å). Despite low-sequence homology, the well-defined structure carries an overall helical fold similar to homeodomain DNA-binding proteins but lacks their archetypical, minor groove-binding N-terminal extension. Sequence comparison indicates that this N-terminal homeodomain-like fold is a common hallmark of metazoan RecQL4 and yeast Sld2 DNA replication initiation factors. RecQL4_N54 binds DNA without noticeable sequence specificity yet with apparent preference for branched over double-stranded (ds) or single-stranded (ss) DNA. NMR chemical shift perturbation observed upon titration with Y-shaped, ssDNA and dsDNA shows a major contribution of helix α3 to DNA binding, and additional arginine side chain interactions for the ss and Y-shaped DNA.

PubMed: 22730300
DOI: 10.1093/nar/gks591

Experimental method

SOLUTION NMR