2VI6

Crystal Structure of the Nanog Homeodomain

Summary for 2VI6

• Entry DOI: 10.2210/pdb2vi6/pdb
• Descriptor: HOMEOBOX PROTEIN NANOG (2 entities in total)
• Functional Keywords: homeodomain, dna-binding, transcription, transcription factor, developmental protein, transcription regulation, nanog, nucleus, homeobox, activator, repressor
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Nucleus: Q80Z64
• Total number of polymer chains: 8
• Total formula weight: 60807.63

Authors

Jauch, R.,Ng, C.K.L.,Saitakendu, K.S.,Stevens, R.C.,Kolatkar, P.R. (deposition date: 2007-11-28, release date: 2008-01-15, Last modification date: 2024-11-06)

Primary citation

Jauch, R.,Ng, C.K.L.,Saitakendu, K.S.,Stevens, R.C.,Kolatkar, P.R.
Crystal Structure and DNA Binding of the Homeodomain of the Stem Cell Transcription Factor Nanog.
J.Mol.Biol., 376:758-, 2008

PubMed Abstract: The transcription factor Nanog is an upstream regulator in early mammalian development and a key determinant of pluripotency in embryonic stem cells. Nanog binds to promoter elements of hundreds of target genes and regulates their expression by an as yet unknown mechanism. Here, we report the crystal structure of the murine Nanog homeodomain (HD) and analysis of its interaction with a DNA element derived from the Tcf3 promoter. Two Nanog amino acid pairs, unique among HD sequences, appear to affect the mechanism of nonspecific DNA recognition as well as maintain the integrity of the structural scaffold. To assess selective DNA recognition by Nanog, we performed electrophoretic mobility shift assays using a panel of modified DNA binding sites and found that Nanog HD preferentially binds the TAAT(G/T)(G/T) motif. A series of rational mutagenesis experiments probing the role of six variant residues of Nanog on its DNA binding function establish their role in affecting binding affinity but not binding specificity. Together, the structural and functional evidence establish Nanog as a distant member of a Q50-type HD despite having considerable variation at the sequence level.

PubMed: 18177668
DOI: 10.1016/J.JMB.2007.11.091

Experimental method

X-RAY DIFFRACTION (2.6 Å)