Tumour necrosis factor is in equilibrium with a trimeric molten globule at low pH.
The reversible acid denaturation of tumour necrosis factor, TNF alpha, a trimeric, all-beta protein, leads to significant conformational changes within the molecule. A change in far UV CD spectra reveals a shift in the secondary structure content of the protein, with alpha-helical structure being induced. Loss of ellipticity in the near UV reflects a loss of tertiary interactions. This form of TNF is both compact and trimeric, as revealed by fluorescence anisotropy and sedimentation velocity analysis, respectively. Acid-denatured TNF therefore possesses the defining features of the molten globule intermediate while retaining the ability of the still incompletely folded monomers to exhibit the surface specificity necessary for maintaining the trimeric state.
Hlodan
R
R
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, UK.
Pain
R H
RH
D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
D014409:Tumor Necrosis Factor-alpha