Corticosteroid-binding globulin (CBG) reactive centre loop antibodies and surface plasmon resonance interrogate the proposed heat dependent "flip-flop" mechanism of human CBG

The Journal of Steroid Biochemistry and Molecular Biology
J G LewisPeter A Elder

Abstract

Corticosteroid-binding globulin (CBG) is the predominant carrier of cortisol in circulation and is a non-inhibitory member of the serpin superfamily of serine protease inhibitors. In the stressed or "S" conformation, CBG possesses an intact exposed reactive centre loop (RCL) that can be irreversibly cleaved by elastase released from activated human neutrophils whereupon it adopts a relaxed or "R" conformation. The latter conformation has decreased affinity for cortisol, allowing the release of the majority of cortisol at sites of inflammation. Recently there has been speculation that mild increments in heat such as found in pyrexia (39-40°C) may also induce a reversible "flip-flop" of the RCL into the body of the protein structure, without cleavage, facilitating a reversible temperature-dependent release of cortisol. Here we raised a new monoclonal antibody to the RCL of human CBG and used this in concert with an existing RCL antibody and show by surface plasma resonance that, at temperatures up to 40°C, the RCL of purified CBG and the RCL of CBG in intact plasma is accessible to these two antibodies. Together, the epitopes of these antibodies span 11 consecutive amino acids (STGVTLNLTSK) of the 18 residues of the RCL. This ade...Continue Reading

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Jan 16, 2014·Molecular and Cellular Endocrinology·John G Lewis, Peter A Elder

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Citations

Jul 16, 2016·Pharmacology & Therapeutics·David HenleyRobin Carrell
Feb 9, 2017·Stress : the International Journal on the Biology of Stress·Marni Anne NenkeDavid James Torpy
Jul 31, 2018·Expert Review of Endocrinology & Metabolism·Emily J MeyerDavid J Torpy

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