3GV5

Human DNA polymerase iota in complex with T template DNA and incoming ddADP

Summary for 3GV5

• Entry DOI: 10.2210/pdb3gv5/pdb
• Related: 3GV7 3GV8
• Descriptor: DNA polymerase iota, 5'-D(*GP*TP*GP*GP*AP*TP*GP*AP*G)-3', 5'-D(P*CP*AP*TP*TP*CP*TP*CP*AP*TP*CP*CP*AP*C)-3', ... (7 entities in total)
• Functional Keywords: y-family polymerase, polymerase iota, error prone replication, dna damage, dna repair, dna replication, dna synthesis, dna-binding, dna-directed dna polymerase, magnesium, metal-binding, mutator protein, nucleotidyltransferase, nucleus, schiff base, transferase, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9UNA4
• Total number of polymer chains: 6
• Total formula weight: 109748.08

Authors

Kirouac, K.N.,Ling, H. (deposition date: 2009-03-30, release date: 2009-06-02, Last modification date: 2024-10-30)

Primary citation

Kirouac, K.N.,Ling, H.
Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase iota
Embo J., 28:1644-1654, 2009

PubMed Abstract: Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP and dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity.

PubMed: 19440206
DOI: 10.1038/emboj.2009.122

Experimental method

X-RAY DIFFRACTION (2 Å)