5FLV

Crystal structure of NKX2-5 and TBX5 bound to the Nppa promoter region

Summary for 5FLV

• Entry DOI: 10.2210/pdb5flv/pdb
• Related: 5FM6 5FM7
• Descriptor: HOMEOBOX PROTEIN NKX-2.5, T-BOX TRANSCRIPTION FACTOR TBX5, 5'-D(*TP*CP*TP*TP*CP*TP*CP*AP*CP*AP*CP*CP*TP*TP *TP*GP*AP*AP*GP*TP*GP*G)-3', 5'-D(*AP*CP*CP*AP*CP*TP*TP*CP*AP*AP*AP*GP*GP*TP *GP*TP*GP*AP*GP*AP*AP*G)-3', ... (4 entities in total)
• Functional Keywords: transcription
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Cellular location: Nucleus : P42582
• Total number of polymer chains: 12
• Total formula weight: 186190.66

Authors

Stirnimann, C.U.,Glatt, S.,Mueller, C.W. (deposition date: 2015-10-28, release date: 2016-02-10, Last modification date: 2024-01-10)

Primary citation

Luna-Zurita, L.,Stirnimann, C.U.,Glatt, S.,Kaynak, B.L.,Thomas, S.,Baudin, F.,Samee, M.A.H.,He, D.,Small, E.M.,Mileikovsky, M.,Nagy, A.,Holloway, A.K.,Pollard, K.S.,Muller, C.W.,Bruneau, B.G.
Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.
Cell(Cambridge,Mass.), 164:999-, 2016

PubMed Abstract: Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation.

PubMed: 26875865
DOI: 10.1016/J.CELL.2016.01.004

Experimental method

X-RAY DIFFRACTION (3.005 Å)