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Purine-rich element binding protein alphaPurine-rich element binding protein alpha

<StructureSection load='5fgp' size='340' side='right' caption=Drosophila Purα intramolecular domain (purple: PUR repeat I, orange: PUR repeat II) in complex with DNA (green). X-ray diffraction, 2Å resolution (5fgp). scene='78/786627/5fgp_intro/8'>

IntroductionIntroduction

Purine-rich element binding protein alpha (Purα or PurA) is a transcription factor with a molecular weight of ~35 kDa encoded by the PURA gene. It possesses ATP-independent dsDNA unwinding activity, and is known to bind sequence-specific purine-rich regions of ssDNA and ssRNA, recognizing GGN motifs. Purα is a member of the PUR family of proteins, which includes Purβ and two isoforms of Purγ. In its functional dimeric form Purα is known to repress expression of smooth muscle alpha actin (SMαA) encoded by the Acta2 gene. It is also known to be involved in DNA replication and cell cycle regulation as well as mRNA translation. It plays a crucial role in nervous system development, and mutations in Purα have been implicated in two neurological diseases: PURA syndrome and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) (see Disease section).

StructureStructure

A PUR domain is analogous to a left-handed handshake. PUR repeat I-II represented from 5fgp.

Purα is a Purα functions as a dimer composed of two intramolecular domains and one intermolecular domain. The Purα monomer contains three semi-conserved repeated amino acid sequences, named in order from N->C: PUR repeats I, II, and III. These repeats fold to form two domains: associating to form the I-II domain or “intramolecular domain”, while facilitates dimerization through association with a repeat III from a second Purα monomer or repeat III of Purβ. Each PUR repeat is connected by flexible linker regions. Each PUR repeat contains a beta-sheet composed of four beta-strands, followed by a single alpha-helix.

The domains of Purα have been described as "Whirly-like" folds because of their structural similarity to the DNA-binding Whirly class of proteins found in plants.

FunctionFunction

High-affinity nucleic acid-binding function is dependent on Purα dimerization. Purα forms homodimers in addition to heterodimers with Purβ. PurA is known to repress various genes including , Y57 (repeat I) and F145 (repeat II) have been implicated in the DNA unwinding activity of PurA.

DevelopmentDevelopment

Purα expression is highest during fetal development, specifically in the brain, spinal cord, and genitalia. In adult humans Purα expression decreases, and is restricted primarily to the brain and testes.

Tissue SpecificityTissue Specificity

While Purα is a ubiquitously expressed protein in all cell types, it is generally found at low levels in most tissues. However, in adult humans and mice Purα expression is highest in the brain and spinal cord, and to a lesser extent in the testes. Purα has been shown to be upregulated in cardiac myocyte gap junctions following heart transplant in mice, colocalizing with actin.

DiseaseDisease

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