Abstract
During the last decade a growing amount of evidence has been obtained, supporting the role of the beta-clamshell family of intracellular lipid binding proteins (iLBPs) not only in the translocation of lipophilic molecules but also in lipid mediated signalling and metabolism. Given the central role of lipids in physiological processes, it is essential to have detailed knowledge on their interactions with cognate binding proteins. Structural and dynamical aspects of the binding mechanisms have been widely investigated by means of NMR spectroscopy, docking and molecular dynamics simulation approaches. iLBPs share a stable beta-barrel fold, delimiting an internal cavity capable of promiscuous ligand binding and display significant flexibility at the putative ligand portal. These features make this class of proteins good scaffolds to build host-guest systems for applications in nanomedicine and nanomaterials.
Highlights
The intracellular lipid binding protein family [,2], performed to assess the role of ileal bile acid binding proteins (BABPs) using mice with global composed of phylogenetically related low molecular weight proteins, FXR deficiency, which are deficient in ileal BABP [6, 2]
BABPs, to the other members of the intestine circulation but its exact role in bile acid transport and intracellular lipid binding proteins (iLBPs) family, are characterized by the presence of approximately 25 metabolism could not be properly assessed because FXR is needed for amino acid residues folded into ten antiparallel beta-strands that form a clamshell-like structure, capped by a pair of alpha-helices, delimiting an internal cavity for ligand binding [3]
We proved that the human liver fatty acid binding protein (FABP) may act as a bile acids carrier, contributing, together with the known human ileal BABP [ 7], to the regulation of bile acid metabolism [ 6, 8]
Summary
The intracellular lipid binding protein (iLBP) family [ ,2], performed to assess the role of ileal BABP using mice with global composed of phylogenetically related low molecular weight proteins, FXR deficiency, which are deficient in ileal BABP [6, 2]. Employing a gain-of-function approach, the non-cooperative chicken ileal BABP was turned into a cooperative protein, designing appropriate mutants and showing, on the basis of NMR data coupled to molecular dynamics simulations, that the cooperative binding mechanism requires the presence of few latch residues, located in the inner protein cavity, that click into their final conformation upon ligand addition and stabilise an extended communication network necessary for establishing energetic coupling between binding sites [37] In this context, 2D line shape analysis [38] applied to a titration experiment of liver BABP, in the presence of different concentrations of the binding partner (GCDA), provided information on the effect of ligand binding on the two adjacent nuclei ( H and 5N) throughout the entire titration. BABP: a versatile bio-host system carbonyl-phenyl group contribute to protein-dye stability, driving the orientation of the ligand within the protein cavity
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