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Functional Evolution of BRCT Domains from Binding DNA to Protein

Authors
Publication Date
Keywords
  • Factor-C P140
  • Phosphopeptide-Binding
  • Structure Prediction
  • Conserved Domains
  • Crystal-Structure
  • Repair Proteins
  • Damage
  • Region
  • Repeats
  • Ligase
  • Biological Specimen Preparation
  • Damage
  • Region
  • 晶癖
  • Crystal Structure
  • Specimen Preparation
  • Biological Techniques
  • Biophysical Instrumentation
  • Biophysical Techniques
  • Crystal Faces
  • Crystal Cleavage
  • Faces (Crystal)
  • Crystal Morphology
  • Crystal Habit
  • Morphology
  • Crystal
  • Atomic Structure
  • Crystals
  • Bravais Lattice
  • Crystal Atomic Structure
  • Crystal Lattice Structures
  • Lattice Structure
  • Crystals
  • Point Groups
  • Structure Factors (Crystals)
  • Crystal Symmetry
  • Sample Holders
  • Specimen Holders
  • Microtomes
  • Sample Preparation
  • Crystallography
  • Kristallstruktur
  • Structure Cristalline
  • Crystalline Tructure
  • Crystalline Structure
  • 晶体结构
  • Crystal Orientation
  • Crystallinity
  • Packing (Crystal Density)
  • 损伤
Disciplines
  • Biology

Abstract

The BRCT domain (BRCA1 C-terminal domain) is an important signaling and protein targeting motif in the DNA damage response system. The BRCT domain, which mainly occurs as a singleton (single BRCT) or tandem pair (double BRCT), contains a phosphate-binding pocket that can bind the phosphate from either the DNA end or a phosphopeptide. In this work, we performed a database search, phylogeny reconstruction, and phosphate-binding pocket comparison to analyze the functional evolution of the BRCT domain. We identified new BRCT-containing proteins in bacteria and eukaryotes, and found that the number of BRCT-containing proteins per genome is correlated with genome complexity. Phylogeny analyses revealed that there are two groups of single BRCT domains (sGroup I and sGroup II) and double BRCT domains (dGroup I and dGroup II). These four BRCT groups differ in their phosphate-binding pockets. In eukaryotes, the evolution of the BRCT domain can be divided into three phases. In the first phase, the sGroup I BRCT domain with the phosphate-binding pocket that can bind the phosphate of nicked DNA invaded eukaryotic genome. In the second phase, the phosphate-binding pocket changed from a DNA-binding type to a protein-binding type in sGroup II. The tandem duplication of sGroup II BRCT domain gave birth to double BRCT domain, from which two structurally and functionally distinct groups were evolved. The third phase is after the divergence between animals and plants. Both sGroup I and sGroup II BRCT domains originating in this phase lost the phosphate-binding pocket and many evolved protein-binding sites. Many dGroup I members were evolved in this stage but few dGroup II members were observed. The results further suggested that the BRCT domain expansion and functional change in eukaryote may be driven by the evolution of the DNA damage response system.

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