Chicken ileal bile acid binding protein: a promising target of investigation to understand binding cooperativity across the protein family
Articolo
Data di Pubblicazione:
2010
Citazione:
Chicken ileal bile acid binding protein: a promising target of investigation to understand binding cooperativity across the protein family / M. Guariento, M. Assfalg, S. Zanzoni, D. Fessas, R. Longhi, H. Molinari. - In: BIOCHEMICAL JOURNAL. - ISSN 0264-6021. - 425:2(2010), pp. 413-424. [10.1042/BJ20091209]
Abstract:
Protein–bile acid interactions are crucial microscopic events at
the basis of both physiological and pathological biochemical
pathways. BABPs (bile-acid-binding proteins) are intracellular
transporters able to bind ligands with different stoichiometry,
selectivity and co-operativity. The molecular determinants and
energetics of interaction are the observables that connect
the microscopic to the macroscopic frameworks. The present
paper addresses the study and proposes a mechanism for
the multi-site interaction of bile acids with chicken I-BABP
(ileal BABP) with the aim of elucidating the determinants
of ligand binding in comparison with homologous proteins
from different species and tissues. A thermodynamic binding
model describing two independent consecutive binding sites is
derived from isothermal titration calorimetry experiments and
validated on the basis of both protein-observed and ligandobserved
NMR titration data. It emerges that a singly bound
protein is relatively abundant at low ligand/protein molar ratios
assessing the absence of strong co-operativity. Both the measured
energetics of binding and the distributed protein chemical-shift
perturbations are in agreementwith a first binding event triggering
a global structural rearrangement. The enthalpic and entropic
contributions associated with binding of the first ligand indicate
that the interaction increases stability and order of the bound
protein. The results described in the present study point to the
presence of a protein scaffold which is able to establish long-range
communication networks, but does not manifest positive-binding
co-operativity, as observed for the human protein. We consider
chicken I-BABP a suitable model to address the molecular
basis for a gain-of-function on going from non-mammalian to
mammalian species.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
M. Guariento, M. Assfalg, S. Zanzoni, D. Fessas, R. Longhi, H. Molinari
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