Homology and structure-function correlations between alpha 1-acid glycoprotein and serum retinol-binding protein and its relatives.
Although the serum protein alpha 1-acid glycoprotein (AGP) or orosomucoid has been extensively studied, its relationships with other proteins have been controversial and its precise physiological function has remained unclear. It is shown here that AGP is significantly similar in amino acid sequence and in the locations of introns in its structural gene to members of a protein superfamily that includes serum retinol-binding protein (RBP), beta-lactoglobulin (LG), alpha 2u-globulin, and protein HC (alpha 1-microglobulin). The view that the three-dimensional structure of AGP is closely similar to the published structures of RBP and LG is supported by its homology with these proteins, similarities in disulfide bond arrangements, and its secondary structure profile, predicted from the amino acid sequence. The relationship of AGP with this particular protein family indicates that its well-characterized ability to bind lipophilic drugs and certain steroids is a reflection of its true biological role. It is proposed that AGP and the other members of this extensive group of proteins should be designated lipocalins to reflect a common ability to bind lipophiles by enclosure within their structures in a manner that minimizes solvent contact.
D000595:Amino Acid Sequence; D000818:Animals; D066246:ErbB Receptors / Q000235:genetics; D005796:Genes; D006801:Humans; D009961:Orosomucoid / Q000235:genetics* / Q000502:physiology; D011487:Protein Conformation; D051381:Rats; D012177:Retinol-Binding Proteins / Q000235:genetics* / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
D009961:Orosomucoid; D012177:Retinol-Binding Proteins; D066246:ErbB Receptors