The complex interplay between ligand binding and conformational structure of the folate binding protein (folate receptor): Biological perspectives

Jan Holm, Susanne W Bruun, Steen I Hansen

6 Citationer (Scopus)

Abstract

This review analyzes how interplay between folate binding and changes in folate binding protein (FBP) conformation/self-association affects the biological function of FBP. Concentration-dependent, reversible self-association of hydrophobic apo-FBP at pI=7.4 is associated with decreased affinity for folate, probably due to shielding of binding sites between interacting hydrophobic patches. Titration with folate removes apo-monomers, favoring dissociation of self-associated apo-FBP into apo-monomers. Folate anchors to FBP through a network of hydrogen bonds and hydrophobic interactions, and the binding induces a conformational change with formation of hydrophilic and stable holo-FBP. Holo-FBP exhibits a ligand-mediated concentration-dependent self-association into multimers of great thermal and chemical stability due to strong intermolecular forces. Both ligand and FBP are thus protected against biological/physicochemical decomposition. In biological fluids with low FBP concentrations, e.g., saliva, semen and plasma, hydrophobic apo-monomers and hydrophilic holo-monomers associate into stable asymmetrical complexes with aberrant binding kinetics unless detergents, e.g., cholesterol or phospholipids are present.

OriginalsprogEngelsk
TidsskriftBiochimica et Biophysica Acta
Vol/bind1854
Udgave nummer10 Pt A
Sider (fra-til)1249-59
Antal sider11
ISSN0006-3002
DOI
StatusUdgivet - okt. 2015

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