General Information
The transcription factor, NKX2.5 is one of many proteins classified as a homeodomain, and functions to regulate structural development in eukaryotes. These proteins share a characteristic evolutionarily conserved fold containing three alpha-helices. [1]. DNA-binding is mediated through the insertion of the c-terminal side into the major groove, allowing for base-reside interactions. This allows homeodomains to locate and bind specific DNA sequences, leading to transcriptional activation or repression [2]. The homeodomain of NKX2.5 is flanked by both a N and C-terminal regulatory domain. This puts the biological protein at 324 residues with the homeodomain consisting of residues 138-197 [3]
Research into the structure and function of NKX2.5 has mainly been focused on the DNA-binding homeodomain, as mutations in this region have been linked to specific diseases [4]. This page will focus on the specific interactions of the homeodomain of NKX2.5 with DNA, and how these interactions relate to one of the transcription factor's primary function - heart development.
Clinical Relevance
In the case of NKX2.5, the protein works in conjunction with multiple other transcription factors during cardiogenesis [5],[6]. Recently, research has been focused on NKX2.5 as mutations in the DNA binding residues, and structural support residues of the protein have been linked to congenital heart disease. Specifically, NKX2.5 mutations have been linked to etiologies involving both atrial and septal defects, deficient atrioventricular node conduction, and more complex mutations such as Tetralogy of Fallot and Hypoplastic Left Heart Syndrome [7],[4],[8]. These phenotypes are speculated to arise as a result of decreased
Protein / DNA Interactions
Scene
Mutational Analysis
Protein / DNA interactions
Structural highlights
