2V95

Structure of Corticosteroid-Binding Globulin in complex with Cortisol

Replaces:  2V6D

Summary for 2V95

• Entry DOI: 10.2210/pdb2v95/pdb
• Descriptor: CORTICOSTEROID-BINDING GLOBULIN, (11alpha,14beta)-11,17,21-trihydroxypregn-4-ene-3,20-dione (3 entities in total)
• Functional Keywords: transport protein, cbg, rcl, serpin, secreted, transport, glycoprotein, lipid-binding, glucocorticoids, steroid-binding, steroid transporter, corticosteroid-binding globulin transport protein
• Biological source: RATTUS NORVEGICUS (RAT)
• Cellular location: Secreted: P31211
• Total number of polymer chains: 1
• Total formula weight: 42251.92

Authors

Klieber, M.A.,Muller, Y.A. (deposition date: 2007-08-21, release date: 2007-09-04, Last modification date: 2023-12-13)

Primary citation

Klieber, M.A.,Underhill, C.,Hammond, G.L.,Muller, Y.A.
Corticosteroid-Binding Globulin: Structural Basis for Steroid Transport and Proteinase-Triggered Release
J.Biol.Chem., 282:29594-, 2007

PubMed Abstract: Corticosteroid-binding globulin (CBG) is a serine proteinase inhibitor (serpin) family member that transports glucocorticoids in blood and regulates their access to target cells. The 1.9A crystal structure of rat CBG shows that its steroid-binding site resembles the thyroxin-binding site in the related serpin, thyroxin-binding globulin, and mutagenesis studies have confirmed the contributions of key residues that constitute the steroid-binding pocket. Unlike thyroxin-bound thyroxin-binding globulin, the cortisol-bound CBG displays an "active" serpin conformation with the proteinase-sensitive, reactive center loop (RCL) fully expelled from the regulatory beta-sheet A. Moreover, the CBG structure allows us to predict that complete insertion of the proteolytically cleaved RCL into the serpin fold occurs in concert with a displacement and unwinding of helix D that would disrupt the steroid-binding site. This allosteric coupling between RCL positioning and occupancy of the CBG steroid-binding site, which resembles the ligand (glycosamino-glycan)-dependent activation of the thrombin inhibitory serpins heparin cofactor II and anti-thrombin RCLs, ensures both optimal recognition of CBG by target proteinases and efficient release of steroid to sites of action.

PubMed: 17644521
DOI: 10.1074/JBC.M705014200

Experimental method

X-RAY DIFFRACTION (1.93 Å)