Solution structure, hydrodynamics and thermodynamics of the UvrB C-terminal domain

J Biomol Struct Dyn. 2001 Oct;19(2):219-36. doi: 10.1080/07391102.2001.10506734.

Abstract

The solution structure, thermodynamic stability and hydrodynamic properties of the 55-residue C-terminal domain of UvrB that interacts with UvrC during excision repair in E. coli have been determined using a combination of high resolution NMR, ultracentrifugation, 15N NMR relaxation, gel permeation, NMR diffusion, circular dichroism and differential scanning calorimetry. The subunit molecular weight is 7,438 kDa., compared with 14.5+/-1.0 kDa. determined by equilibrium sedimentation, indicating a dimeric structure. The structure determined from NMR showed a stable dimer of anti-parallel helical hairpins that associate in an unusual manner, with a small and hydrophobic interface. The Stokes radius of the protein decreases from a high plateau value (ca. 22 A) at protein concentrations greater than 4 microM to about 18 A at concentrations less than 0.1 microM. The concentration and temperature-dependence of the far UV circular dichroism show that the protein is thermally stable (Tm ca. 71.5 degrees C at 36 microM). The simplest model consistent with these data was a dimer dissociating into folded monomers that then unfolds co-operatively. The van't Hoff enthalpy and dissociation constant for both transition was derived by fitting, with deltaH1=23 kJ mol(-1). K1(298)=0.4 microM and deltaH2= 184 kJ mol(-1). This is in good agreement with direct calorimetric analysis of the thermal unfolding of the protein, which gave a calorimetric enthalpy change of 181 kJ mol(-1) and a van't Hoff enthalpy change of 354 kJ mol(-1), confirming the dimer to monomer unfolding. The thermodynamic data can be reconciled with the observed mode of dimerisation. 15N NMR relaxation measurements at 14.1 T and 11.75 T confirmed that the protein behaves as an asymmetric dimer at mM concentrations, with a flexible N-terminal linker for attachment to the remainder of the UvrB protein. The role of dimerisation of this domain in the excision repair mechanism is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calorimetry, Differential Scanning
  • Circular Dichroism
  • DNA Helicases / chemistry*
  • DNA Helicases / genetics
  • DNA Repair
  • Dimerization
  • Endodeoxyribonucleases / chemistry
  • Endodeoxyribonucleases / genetics
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins*
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Protein Denaturation
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Solutions
  • Static Electricity
  • Thermodynamics

Substances

  • Escherichia coli Proteins
  • Solutions
  • UvrB protein, E coli
  • Endodeoxyribonucleases
  • UvrC protein, E coli
  • DNA Helicases