4J9P: Human Dna Polymerase Eta-dna Postinsertion Binary Complex With Ta Base Pair

Somatic hypermutation is programmed base substitutions in the variable regions of Ig genes for high-affinity antibody generation. Two motifs, RGYW and WA (R, purine; Y, pyrimidine; W, A or T), have been found to be somatic hypermutation hotspots. Overwhelming evidence suggests that DNA polymerase eta (Pol eta) is responsible for converting the WA motif to WG by misincorporating dGTP opposite the templating T. To elucidate the molecular mechanism, crystal structures and kinetics of human Pol eta substituting dGTP for dATP in four sequence contexts, TA, AA, GA, and CA, have been determined and compared. The T:dGTP wobble base pair is stabilized by Gln-38 and Arg-61, two uniquely conserved residues among Pol eta. Weak base paring of the W (T:A or A:T) at the primer end and their distinct interactions with Pol eta lead to misincorporation of G in the WA motif. Between two WA motifs, our kinetic and structural data indicate that A-to-G mutation occurs more readily in the TA context than AA. Finally, Pol eta can extend the T:G mispair efficiently to complete the mutagenesis.
PDB ID: 4J9PDownload
MMDB ID: 109683
PDB Deposition Date: 2013/2/16
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4J9P: trimeric; determined by author and by software (PISA)
Molecular Components in 4J9P
Label Count Molecule
Protein (1 molecule)
DNA Polymerase ETA(Gene symbol: POLH)
Molecule annotation
Nucleotides(2 molecules)
DNA (5'-d(*c*ap*tp*tp*ap*tp*gp*ap*cp*gp*cp*t)-3')
Molecule annotation
DNA (5'-d(*tp*ap*gp*cp*gp*tp*cp*ap*tp*a)-3')
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB