TY - JOUR
T1 - Ligand binding and self-association cooperativity of β-lactoglobulin
AU - Gutiérrez-Magdaleno, Gabriel
AU - Bello, Martiniano
AU - Portillo-Téllez, M. Carmen
AU - Rodríguez-Romero, Adela
AU - García-Hernández, Enrique
PY - 2013/2
Y1 - 2013/2
N2 - Unlike most small globular proteins, lipocalins lack a compact hydrophobic core. Instead, they present a large central cavity that functions as the primary binding site for hydrophobic molecules. Not surprisingly, these proteins typically exhibit complex structural dynamics in solution, which is intricately modified by intermolecular recognition events. Although many lipocalins are monomeric, an increasing number of them have been proven to form oligomers. The coupling effects between self-association and ligand binding in these proteins are largely unknown. To address this issue, we have calorimetrically characterized the recognition of dodecyl sulfate by bovine β-lactoglobulin, which forms weak homodimers at neutral pH. A thermodynamic analysis based on coupled-equilibria revealed that dimerization exerts disparate effects on the ligand-binding capacity of β-lactoglobulin. Protein dimerization decreases ligand affinity (or, reciprocally, ligand binding promotes dimer dissociation). The two subunits in the dimer exhibit a positive, entropically driven cooperativity. To investigate the structural determinants of the interaction, the crystal structure of β-lactoglobulin bound to dodecyl sulfate was solved at 1.64 Å resolution.
AB - Unlike most small globular proteins, lipocalins lack a compact hydrophobic core. Instead, they present a large central cavity that functions as the primary binding site for hydrophobic molecules. Not surprisingly, these proteins typically exhibit complex structural dynamics in solution, which is intricately modified by intermolecular recognition events. Although many lipocalins are monomeric, an increasing number of them have been proven to form oligomers. The coupling effects between self-association and ligand binding in these proteins are largely unknown. To address this issue, we have calorimetrically characterized the recognition of dodecyl sulfate by bovine β-lactoglobulin, which forms weak homodimers at neutral pH. A thermodynamic analysis based on coupled-equilibria revealed that dimerization exerts disparate effects on the ligand-binding capacity of β-lactoglobulin. Protein dimerization decreases ligand affinity (or, reciprocally, ligand binding promotes dimer dissociation). The two subunits in the dimer exhibit a positive, entropically driven cooperativity. To investigate the structural determinants of the interaction, the crystal structure of β-lactoglobulin bound to dodecyl sulfate was solved at 1.64 Å resolution.
KW - SDS recognition
KW - allostery
KW - crystallography
KW - isothermal titration calorimetry
KW - lipocalin
KW - protein-lipid interaction
UR - http://www.scopus.com/inward/record.url?scp=84872698938&partnerID=8YFLogxK
U2 - 10.1002/jmr.2249
DO - 10.1002/jmr.2249
M3 - Artículo
SN - 0952-3499
VL - 26
SP - 67
EP - 75
JO - Journal of Molecular Recognition
JF - Journal of Molecular Recognition
IS - 2
ER -