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Published on: September 21, 2011
Hormone binding globulins undergo serpin conformational change in inflammation
P A Pemberton1, P E Stein, M B Pepys
1Department of Haematology, University of Cambridge, UK.
Nature
|November 17, 1988
Summary
Thyroxine binding globulin (TBG) and cortisol binding globulin (CBG) retain a stressed structure, typical of serine protease inhibitors (serpins). This structure facilitates altered hormone delivery to inflammatory sites, despite lacking inhibitory function.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Thyroxine binding globulin (TBG) and cortisol binding globulin (CBG) are identified as members of the serine protease inhibitor (serpin) superfamily.
- Despite their superfamily classification, TBG and CBG function as hormone transport proteins, with no apparent retained protease inhibitory activity.
Purpose of the Study:
- To investigate the structural conformation of TBG and CBG in relation to their serpin origins.
- To explore the functional implications of their retained native structure for hormone transport and delivery.
Main Methods:
- Structural analysis of TBG and CBG.
- Comparative analysis with known serpin inhibitor structures.
- Investigation of the stressed-to-relaxed (S-R) conformational transition.
Main Results:
- TBG and CBG possess the stressed native structure characteristic of active serpin inhibitors.
- Evidence suggests the S-R transition in TBG and CBG is functionally adapted for modified hormone delivery.
- This adaptation is particularly relevant at inflammatory sites.
Conclusions:
- The complex serpin framework in TBG and CBG is not merely for transport but is functionally adapted.
- The retained stressed conformation and its transition dynamics are key to altered hormone delivery mechanisms.
- This finding offers new insights into the evolution and function of serpins in non-inhibitory roles.
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