Mapping DNA-binding domains of the autoimmune regulator protein

Sharad B Purohit, Pradeep G. Kumar, Malini Laloraya, Jin-Xiong She

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The human autoimmune regulator (AIRE) gene encodes a putative DNA-binding protein, which is mutated in patients affected by the autoimmune polyglandular syndrome type 1 or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. We have recently reported that AIRE can bind to two different DNA sequence motifs, suggesting the existence of at least two DNA-binding domains in the AIRE protein. By expressing a series of recombinant AIRE protein fragments, we demonstrate here that the two well-known plant homeodomains (PHD) domains in AIRE can bind to the ATTGGTTA sequence motif. The first ATTGGTTA-binding domain is mapped to amino acids 299-355 and the second ATTGGTTA-binding domain to amino acids 434-475. Furthermore, the SAND domain of AIRE is shown to bind to TTATTA motif. Results presented herein show that the residues at position 189-196 of AIRE (QRAVAMSS) are required for its binding to the TTATTA motif. The required sequence for DNA binding in the SAND domain of AIRE is remarkably different from other SAND-containing proteins such as Sp-100b and NUDR. Data presented in this paper indicate that the two PHD domains contained in AIRE, in addition to the SAND domain, can bind to specific DNA sequence motifs.

Original languageEnglish (US)
Pages (from-to)939-944
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume327
Issue number3
DOIs
StatePublished - Feb 18 2005

Fingerprint

Autoimmune Polyendocrinopathies
Nucleotide Motifs
DNA sequences
DNA
Amino Acids
Proteins
DNA-Binding Proteins
Regulator Genes
Genes

Keywords

  • AIRE
  • APS
  • DNA binding
  • PHD
  • SAND

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mapping DNA-binding domains of the autoimmune regulator protein. / Purohit, Sharad B; Kumar, Pradeep G.; Laloraya, Malini; She, Jin-Xiong.

In: Biochemical and Biophysical Research Communications, Vol. 327, No. 3, 18.02.2005, p. 939-944.

Research output: Contribution to journalArticle

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