Crystal structure of a paired domain-DNA complex at 2.5 A resolution reveals structural basis for Pax developmental mutations.
The 2.5 A resolution structure of a cocrystal containing the paired domain from the Drosophila paired (prd) protein and a 15 bp site shows structurally independent N-terminal and C-terminal subdomains. Each of these domains contains a helical region resembling the homeodomain and the Hin recombinase. The N-terminal domain makes extensive DNA contacts, using a novel beta turn motif that binds in the minor groove and a helix-turn-helix unit with a docking arrangement surprisingly similar to that of the lambda repressor. The C-terminal domain is not essential for prd binding and does not contact the optimized site. All known developmental missense mutations in the paired box of mammalian Pax genes map to the N-terminal subdomain, and most of them are found at the protein-DNA interface.
Xu
W
W
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Rould
M A
MA
Jun
S
S
Desplan
C
C
Pabo
C O
CO
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003461:Crystallography; D004247:DNA / Q000737:chemistry*; D004254:DNA Nucleotidyltransferases / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004330:Drosophila / Q000737:chemistry* / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D018398:Homeodomain Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; C489935:prd protein, Drosophila; D004247:DNA; D004254:DNA Nucleotidyltransferases; C059997:Hin recombinase