Crystal structure of chicken liver basic fatty acid-binding protein complexed with cholic acid.
Two paralogous groups of liver fatty acid-binding proteins (FABPs) have been described: the mammalian type liver FABPs and the basic type (Lb-FABPs) characterized in several vertebrates but not in mammals. The two groups have similar sequences and share a highly conserved three-dimensional structure, but their specificity and stoichiometry of binding are different. The crystal structure of chicken Lb-FABP complexed with cholic acid and that of the apoprotein refined to 2.0 A resolution are presented in this paper. The two forms of the protein crystallize in different space groups, and significant changes are observed between the two conformations. The holoprotein binds two molecules of cholate in the interior cavity, and the contacts observed between the two ligands can help to explain the reason for this stoichiometry of binding. Most of the amino acids involved in ligand binding are conserved in other members of the Lb-FABP family. Since the amino acid sequence of the Lb-FABPs is more similar to that of the bile acid-binding proteins than to that of the L-FABPs, the possibility that the Lb-FABPs might be more appropriately called liver bile acid-binding proteins (L-BABPs) is suggested.
Nichesola
Daniele
D
Laboratorio di Biocristallografía, Dipartimento Scientifico e Tecnologico, Università di Verona, Strada Le Grazie 15, 37134 Verona, Italy.
Perduca
Massimiliano
M
Capaldi
Stefano
S
Carrizo
Maria E
ME
Righetti
Pier Giorgio
PG
Monaco
Hugo L
HL
D000595:Amino Acid Sequence; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002645:Chickens; D019826:Cholic Acid / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D008099:Liver / Q000737:chemistry* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation
D001059:Apoproteins; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; C037643:bile acid binding proteins; D019826:Cholic Acid