Molecular diversity and evolution of the large lipid transfer protein superfamilys⃞

Abstract

Circulatory lipid transport in animals is mediated to a substantial extent by members of the large lipid transfer (LLT) protein (LLTP) superfamily. These proteins, including apolipoprotein B (apoB), bind lipids and constitute the structural basis for the assembly of lipoproteins. The current analyses of sequence data indicate that LLTPs are unique to animals and that these lipid binding proteins evolved in the earliest multicellular animals. In addition, two novel LLTPs were recognized in insects. Structural and phylogenetic analyses reveal three major families of LLTPs: the apoB-like LLTPs, the vitellogenin-like LLTPs, and the microsomal triglyceride transfer protein (MTP)-like LLTPs, or MTPs. The latter are ubiquitous, whereas the two other families are distributed differentially between animal groups. Besides similarities, remarkable variations are also found among LLTPs in their major lipid-binding sites (i.e., the LLT module as well as the predicted clusters of amphipathic secondary structure): variations such as protein modification and number, size, or occurrence of the clusters. Strikingly, comparative research has also highlighted a multitude of functions for LLTPs in addition to circulatory lipid transport. The integration of LLTP structure, function, and evolution reveals multiple adaptations, which have come about in part upon neofunctionalization of duplicated genes. Moreover, the change, exchange, and expansion of functions illustrate the opportune application of lipid-binding proteins in nature. Accordingly, comparative research exposes the structural and functional adaptations in animal lipid carriers and brings up novel possibilities for the manipulation of lipid transport.

Keywords

• phylogeny
• subfunctionalization
• sequence alignment
• clotting protein
• melanin-engaging protein
• microsomal triglyceride transfer protein