title: Acquisition of triacylglycerol transfer activity by microsomal triglyceride transfer protein during evolution.
abstract: Microsomal triglyceride transfer protein (MTP) is essential for the assembly of neutral-lipid-rich apolipoprotein B (apoB) lipoproteins. Previously we reported that the Drosophila MTP transfers phospholipids but does not transfer triglycerides. In contrast, human MTP transfers both lipids. To explore the acquisition of triglyceride transfer activity by MTP, we evaluated amino acid sequences, protein structures, and the biochemical and cellular properties of various MTP orthologues obtained from species that diverged during evolution. All MTP orthologues shared similar secondary and tertiary structures, associated with protein disulfide isomerase, localized to the endoplasmic reticulum, and supported apoB secretion. While vertebrate MTPs transferred triglyceride, invertebrate MTPs lacked this activity. Thus, triglyceride transfer activity was acquired during the transition from invertebrates to vertebrates. Within vertebrates, fish, amphibians, and birds displayed 27%, 40%, and 100% triglyceride transfer activity compared to mammals. We conclude that MTP triglyceride transfer activity first appeared in fish and speculate that the acquisition of triglyceride transfer activity by MTP provided for a significant advantage in the evolution of larger and more complex organisms.
authors.affiliation: Molecular and Cellular Biology Program, School of Graduate Studies, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Rava
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity; D017931:DNA Primers; D019143:Evolution, Molecular; D005455:Fluorescent Antibody Technique; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein