title: Scan-rate-dependent melting transitions of interleukin-1 receptor (type II): elucidation of meaningful thermodynamic and kinetic parameters of aggregation acquired from DSC simulations.
abstract: The role of thermal unfolding as it pertains to thermodynamic properties of proteins and their stability has been the subject of study for more than 50 years. Moreover, exactly how the unfolding properties of a given protein system may influence the kinetics of aggregation has not been fully characterized. In the study of recombinant human Interleukin-1 receptor type II (rhuIL-1R(II)) aggregation, data obtained from size exclusion chromatography and differential scanning calorimetry (DSC) were used to model the thermodynamic and kinetic properties of irreversible denaturation. A break from linearity in the initial aggregation rates as a function of 1/T was observed in the vicinity of the melting transition temperature (T(m) approximately 53.5 degrees C), suggesting significant involvement of protein unfolding in the reaction pathway. A scan-rate dependence in the DSC experiment testifies to the nonequilibrium influences of the aggregation process. A mechanistic model was developed to extract meaningful thermodynamic and kinetic parameters from an irreversibly denatured process. The model was used to simulate how unfolding properties could be used to predict aggregation rates at different temperatures above and below the T(m) and to account for concentration dependence of reaction rates. The model was shown to uniquely identify the thermodynamic parameters DeltaC(P) (1.3 +/- 0.7 kcal/mol-K), DeltaH(m) (74.3 +/- 6.8 kcal/mol), and T(m) with reasonable variances.
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. remmeler@amgen.com
authors.forename: Richard L
authors.initials: RL
authors.lastname: Remmele
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang-van Enk
authors.forename: Vasu
authors.initials: V
authors.lastname: Dharmavaram
authors.forename: David
authors.initials: D
authors.lastname: Balaban
authors.forename: Mark
authors.initials: M
authors.lastname: Durst
authors.forename: Alex
authors.initials: A
authors.lastname: Shoshitaishvili
authors.forename: Hugh
authors.initials: H
authors.lastname: Rand
mesh_terms: D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D007700:Kinetics; D017472:Receptors, Interleukin-1 / Q000737:chemistry*; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
chemical_list: D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins