6PAX

CRYSTAL STRUCTURE OF THE HUMAN PAX-6 PAIRED DOMAIN-DNA COMPLEX REVEALS A GENERAL MODEL FOR PAX PROTEIN-DNA INTERACTIONS

Summary for 6PAX

• Entry DOI: 10.2210/pdb6pax/pdb
• Descriptor: 26 NUCLEOTIDE DNA, HOMEOBOX PROTEIN PAX-6, ... (4 entities in total)
• Functional Keywords: pax, paired domain, transcription, protein-dna interactions, gene regulation-dna complex, gene regulation/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P26367
• Total number of polymer chains: 3
• Total formula weight: 30494.86

Authors

Xu, H.E.,Rould, M.A.,Xu, W.,Epstein, J.A.,Maas, R.L.,Pabo, C.O. (deposition date: 1999-04-22, release date: 1999-07-13, Last modification date: 2024-04-03)

Primary citation

Xu, H.E.,Rould, M.A.,Xu, W.,Epstein, J.A.,Maas, R.L.,Pabo, C.O.
Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding.
Genes Dev., 13:1263-1275, 1999

PubMed Abstract: Pax6, a transcription factor containing the bipartite paired DNA-binding domain, has critical roles in development of the eye, nose, pancreas, and central nervous system. The 2.5 A structure of the human Pax6 paired domain with its optimal 26-bp site reveals extensive DNA contacts from the amino-terminal subdomain, the linker region, and the carboxy-terminal subdomain. The Pax6 structure not only confirms the docking arrangement of the amino-terminal subdomain as seen in cocrystals of the Drosophila Prd Pax protein, but also reveals some interesting differences in this region and helps explain the sequence specificity of paired domain-DNA recognition. In addition, this structure gives the first detailed information about how the paired linker region and carboxy-terminal subdomain contact DNA. The extended linker makes minor groove contacts over an 8-bp region, and the carboxy-terminal helix-turn-helix unit makes base contacts in the major groove. The structure and docking arrangement of the carboxy-terminal subdomain of Pax6 is remarkably similar to that of the amino-terminal subdomain, and there is an approximate twofold symmetry axis relating the polypeptide backbones of these two helix-turn-helix units. Our structure of the Pax6 paired domain-DNA complex provides a framework for understanding paired domain-DNA interactions, for analyzing mutations that map in the linker and carboxy-terminal regions of the paired domain, and for modeling protein-protein interactions of the Pax family proteins.

PubMed: 10346815

Experimental method

X-RAY DIFFRACTION (2.5 Å)