Intra-subunit Disulfide Determines the Conversion and Structural Stability of CRP Isoforms
Chun-Miao Zhang1, Yu-Bo Tan1, Hai-Hong Zhou2
1MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, 730000, People's Republic of China.
Inflammation
|November 25, 2019
Summary
C-reactive protein (CRP) transforms into monomeric CRP (mCRP) through a two-stage process involving subunit dissociation and aggregation. Reduction accelerates these changes, impacting mCRP
Area of Science:
- Biochemistry
- Immunology
- Structural Biology
Background:
- C-reactive protein (CRP) is a key human acute-phase reactant composed of five subunits.
- CRP converts to monomeric CRP (mCRP) at inflammatory sites, enhancing its activity.
- The conformational changes during CRP activation are not fully understood.
Purpose of the Study:
- To investigate the conformational changes during CRP to mCRP conversion.
- To examine the effect of reduction on CRP conformational changes.
- To understand the role of electrostatic interactions in CRP structure.
Main Methods:
- Circular dichroism spectroscopy
- Fluorescence spectroscopy
- Electron microscopy
- Size-exclusion chromatography
- Neoepitope expression
Main Results:
- CRP conversion to mCRP is a two-stage process: subunit dissociation into molten globules, followed by aggregation.
- Reduction accelerates molten globule formation and promotes more compact aggregates.
- Electrostatic interactions significantly stabilize native CRP structure.
Conclusions:
- The conformational changes in dissociated subunits and mCRP aggregation are critical for CRP's biological activities.
- Understanding these structural dynamics provides insights into CRP's inflammatory roles.
- This study elucidates the molecular mechanisms behind CRP activation.
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