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Thermodynamics of Protein Quaternary Structures Interconversion of Human PBGS
Author(s) -
Tang Lei,
Stith Linda,
Jaffe Eileen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a953-c
Subject(s) - random hexamer , histone octamer , dimer , protein quaternary structure , oligomer , chemistry , protein subunit , trimer , affinities , dissociation (chemistry) , crystallography , stereochemistry , biochemistry , organic chemistry , gene , nucleosome , histone
Porphobilinogen synthase (PBGS) constitutes the prototype morpheein system; it is a homo‐oligomeric protein that can exist as an equilibrium of at least two functionally distinct quaternary structure isoforms ( Jaffe 2005 , Trends in Biochem. Sci. 30 : 490 – 497 ). PBGS exhibits a dramatic phylogenetic variation in the propensity to interconvert between morpheein structures, and human PBGS morpheeins are long‐lived, particularly in the absence of turnover ( Tang , L. , et al., 2005 , JBC 280 : 15786 – 15793 ). Wild‐type human PBGS is a homo‐octamer, the naturally occurring F12L variant is a homo‐hexamer, and coexpression of these two proteins in E. coli produces a mixture of heterohexamers and heterooctamers. The unique physical and kinetic characteristics these hetero‐oligomeric proteins allow the demonstration that catalytic turnover promotes the structural interconversion between human PBGS morpheeins, a process that requires dissociation of the oligomer, a structural change at the level of the dimer, and reassociation into the alternate oligomer. Catalytic turnover shifts the morpheein equilibrium toward the octamer and results in accumulation of the Phe12 containing chains in the octamer. The temperature dependence of these processes allow the quantification of the energy requirement for the interconversion of octamer and hexamer. A protein concentration dependence to the specific activity of the hetero‐oligomers supports the notion that morpheein interconversion disassembly and reassembly of subunits and the temperature dependence of this phenomenon also provides important thermodynamic information about the subunit reorganization process. This work is supported by National Institute of Health Grant ES03654 and National Institute of Health Grant CA006927.