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Kinetic and thermodynamic studies reveal chemokine homologues CC11 and CC24 with an almost identical tertiary structure have different folding pathways.

ABSTRACT: BACKGROUND:Proteins with low sequence identity but almost identical tertiary structure and function have been valuable to uncover the relationship between sequence, tertiary structure, folding mechanism and functions. Two homologous chemokines, CCL11 and CCL24, with low sequence identity but similar tertiary structure and function, provide an excellent model system for respective studies. RESULTS:The kinetics and thermodynamics of the two homologous chemokines were systematically characterized. Despite their similar tertiary structures, CCL11 and CCL24 show different thermodynamic stability in guanidine hydrochloride titration, with D50% = 2.20 M and 4.96 M, respectively. The kinetics curves clearly show two phases in the folding/unfolding processes of both CCL11 and CCL24, which suggests the existence of an intermediate state in their folding/unfolding processes. The folding pathway of both CCL11 and CCL24 could be well described using a folding model with an on-pathway folding intermediate. However, the folding kinetics and stability of the intermediate state of CCL11 and CCL24 are obviously different. CONCLUSION:Our results suggest homologous proteins with low sequence identity can display almost identical tertiary structure, but very different folding mechanisms, which applies to homologues in the chemokine protein family, extending the general applicability of the above observation.

SUBMITTER: Ge B

PROVIDER: S-EPMC5596964 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Kinetic and thermodynamic studies reveal chemokine homologues CC11 and CC24 with an almost identical tertiary structure have different folding pathways.

Ge Baosheng B Jiang Xiaoyong X Chen Yao Y Sun Tingting T Yang Qiuxia Q Huang Fang F

BMC biophysics 20170912

<h4>Background</h4>Proteins with low sequence identity but almost identical tertiary structure and function have been valuable to uncover the relationship between sequence, tertiary structure, folding mechanism and functions. Two homologous chemokines, CCL11 and CCL24, with low sequence identity but similar tertiary structure and function, provide an excellent model system for respective studies.<h4>Results</h4>The kinetics and thermodynamics of the two homologous chemokines were systematically ...[more]

PMID: 28919974

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Project description:At the heart of the RNA folding problem is the number, structures, and relationships among the intermediates that populate the folding pathways of most large RNA molecules. Unique insight into the structural dynamics of these intermediates can be gleaned from the time-dependent changes in local probes of macromolecular conformation (e.g. reports on individual nucleotide solvent accessibility offered by hydroxyl radical (()OH) footprinting). Local measures distributed around a macromolecule individually illuminate the ensemble of separate changes that constitute a folding reaction. Folding pathway reconstruction from a multitude of these individual measures is daunting due to the combinatorial explosion of possible kinetic models as the number of independent local measures increases. Fortunately, clustering of time progress curves sufficiently reduces the dimensionality of the data so as to make reconstruction computationally tractable. The most likely folding topology and intermediates can then be identified by exhaustively enumerating all possible kinetic models on a super-computer grid. The folding pathways and measures of the relative flux through them were determined for Mg(2+) and Na(+)-mediated folding of the Tetrahymena thermophila group I intron using this combined experimental and computational approach. The flux during Mg(2+)-mediated folding is divided among numerous parallel pathways. In contrast, the flux during the Na(+)-mediated reaction is predominantly restricted through three pathways, one of which is without detectable passage through intermediates. Under both conditions, the folding reaction is highly parallel with no single pathway accounting for more than 50% of the molecular flux. This suggests that RNA folding is non-sequential under a variety of different experimental conditions even at the earliest stages of folding. This study provides a template for the systematic analysis of the time-evolution of RNA structure from ensembles of local measures that will illuminate the chemical and physical characteristics of each step in the process. The applicability of this analysis approach to other macromolecules is discussed.

Dataset Information

Kinetic and thermodynamic studies reveal chemokine homologues CC11 and CC24 with an almost identical tertiary structure have different folding pathways.

Publications

Kinetic and thermodynamic studies reveal chemokine homologues CC11 and CC24 with an almost identical tertiary structure have different folding pathways.

Similar Datasets

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