A comparison of the folding kinetics and thermodynamics of two homologous fibronectin type III modules.
The homologous ninth and tenth type III modules of human fibronectin share identical topologies and nearly identical core structures. Despite these structural similarities, the refolding characteristics of the two modules, which have a sequence identity of less than 30 %, are very different; in the absence of denaturant the ninth module folds several hundred times more slowly than the tenth and, although both modules contain numerous proline residues, only the ninth exhibits a slow, proline isomerization-limited folding phase. The different folding kinetics of the two modules coincide with a large difference in their thermodynamic stability, with the folding free energy of the tenth being approximately five fold greater than that of the ninth. This may be the reason why the ninth module, unlike the rapidly folding tenth module, is apparently unable to overcome characteristics of the fibronectin type III modules that can slow the folding process. The non-proline-limited folding kinetics are, however, very similar for the two modules when compared under conditions where their overall stabilities are similar. The significance of this finding is discussed in terms of possible determinants of the kinetics of protein folding.
Plaxco
K W
KW
New Chemistry Laboratory and The Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QT, England.
Spitzfaden
C
C
Campbell
I D
ID
Dobson
C M
CM
D000595:Amino Acid Sequence; D005353:Fibronectins / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D007700:Kinetics; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
D005353:Fibronectins; D011993:Recombinant Fusion Proteins; D011392:Proline