G148-GA3: a streptococcal virulence module with atypical thermodynamics of folding optimally binds human serum albumin at physiological temperatures.

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TitleG148-GA3: a streptococcal virulence module with atypical thermodynamics of folding optimally binds human serum albumin at physiological temperatures.
Publication TypeJournal Article
Year of Publication2005
AuthorsRozak, DA, Orban, J, Bryan, PN
JournalBiochim Biophys Acta
Volume1753
Issue2
Pagination226-33
Date Published2005 Dec 1
ISSN0006-3002
KeywordsBacterial Proteins, Binding Sites, Calorimetry, Calorimetry, Differential Scanning, Hot Temperature, Humans, Hydrogen-Ion Concentration, Kinetics, Protein Binding, Protein Denaturation, Protein Folding, Serum Albumin, Streptococcus, Temperature, Thermodynamics, Virulence
Abstract

The third albumin binding domain of streptococcal protein G strain 148 (G148-GA3) belongs to a novel class of prokaryotic albumin binding modules that is thought to support virulence in several bacterial species. Here, we characterize G148-GA3 folding and albumin binding by using differential scanning calorimetry and isothermal titration calorimetry to obtain the most complete set of thermodynamic state functions for any member of this medically significant module. When buffered at pH 7.0 the 46-amino acid alpha-helical domain melts at 72 degrees C and exhibits marginal stability (15 kJ/mol) at 37 degrees C. G148-GA3 unfolding is characterized by small contributions to entropy from non-hydrophobic forces and a low DeltaCp (1.1 kJ/(deg mol)). Isothermal titration calorimetry reveals that the domain has evolved to optimally bind human serum albumin near 37 degrees C with a binding constant of 1.4 x 10 7 M(-1). Analysis of G148-GA3 thermodynamics suggests that the domain experiences atypically small per residue changes in structural dynamics and heat capacity while transiting between folded and unfolded states.

DOI10.1016/j.bbapap.2005.10.005
Alternate JournalBiochim. Biophys. Acta
PubMed ID16290081
Grant ListGM62154 / GM / NIGMS NIH HHS / United States