From Proteopedia

Introduction

TBX3 acts as a repressor and has had its crystal structure solved to 1.7 Å resolution. There are many differences between the solved structure of TBX3 and its homologue, Brachyury. Secondary structures and quaternary contacts are slightly different. TBX3 independently recognises two halves of a palindromic site whereas Brachyury is stabilised via interactions between the two monomers. Despite this, the T-box domain of TBX3 and the T-box domain of Brachyury can be superimposed with a rmsd of 1.3 Å for 167 atoms. See Transcription and RNA Processing.

Crystal structure

PDB ID 1h6f Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
TBX3 dimer complex with DNA and Mg+2 ion, 1h6f
Ligands:
Structural annotation: Resources: CATH : 1H6Fa00, 1H6Fb00 InterPro : Ipr001699, Ipr008967 Pfam : PF00907 SCOP : d1h6fa_, d1h6fb_ UniProt : O15119
Functional annotation: Cellular component: nucleus Biological process: positive regulation of cell proliferation embryonic digit morphogenesis regulation of transcription from RNA polymerase II promoter cell aging negative regulation of myoblast differentiation multicellular organismal development anti-apoptosis follicle-stimulating hormone secretion luteinizing hormone secretion male genitalia development transcription negative regulation of transcription, DNA-dependent regulation of transcription, DNA-dependent skeletal development positive regulation of cell cycle determination of anterior/posterior axis, embryo forelimb morphogenesis female genitalia development embryonic arm morphogenesis organ morphogenesis mammary gland development mesoderm morphogenesis Molecular function: transcription repressor activity DNA binding general transcriptional repressor activity transcription factor activity sequence-specific DNA binding RNA polymerase II transcription factor activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

TBX3 expressed from residues 101 - 291 were viable proteins and were crystallised in space group P2₁2₁2₁. These included two monomers and one DNA duplex in the asymmetric unit. The monomers themselves can be superimposed to give an rmsd of 0.5 Å. The largest differences between the TBX3 crystal structure and the T-box domain of Brachyury is between residues 173 and 184, and between strands F and G. Four residues are inserted between F and G and this adopts a 3₁₀ conformation.

Interaction with DNA

Loops that protrude from one end of the β barrel and the C-terminal helical extension contact both the major and minor grooves of the DNA. Strand B contains residues , and recognises the major groove. Arg130 is the only residue in direct contact with a DNA base in the major groove and recognises N7 and H₂O.O6 of guanine (base pair 5) and the corresponding phosphate. Arg131 interacts with the DNA backbone mediated by water.

gα3 loop interaction with DNA

The gα3 loop spans the major groove. H3 (Tyr264, Gln265 and ) form polar contacts to the DNA backbone and hydrophobic contacts to the ribose moiety. There are similar contacts in the crystal structure of Brachyury.

3₁₀ helix interaction with DNA

The helix 3₁₀C, also present in TBX5, contacts DNA in the minor groove and hence widens it. However, overall the DNA is not bent, as seen in other crystal structures of T-box proteins. The 3₁₀ helix interacts with DNA using (See , , and ).

3D structures of TBX3

T-box proteins

Additional Resources

For additional information, see: Transcription and RNA Processing

Reference

• Coll M, Seidman JG, Muller CW. Structure of the DNA-bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome. Structure. 2002 Mar;10(3):343-56. PMID:12005433