Structure and ligand binding of As-p18, an extracellular fatty acid binding protein from the eggs of a parasitic nematode

REY-BURUSCO, M. FLORENCIA; RIBOLDI-TUNNICLIFFE, ALAN; COOPER, ALAN; SMITH, BRIAN O.; GABRIELSEN, MADS; ROE, ANDREW J.; CÓRSICO, BETINA; GABRIELSEN, MADS; ROE, ANDREW J.; CÓRSICO, BETINA; IBÁÑEZ-SHIMABUKURO, MARINA; FRANCHINI, GISELA R.; GRIFFITHS, KATE; KENNEDY, MALCOLM W.; IBÁÑEZ-SHIMABUKURO, MARINA; FRANCHINI, GISELA R.; GRIFFITHS, KATE; KENNEDY, MALCOLM W.; REY-BURUSCO, M. FLORENCIA; RIBOLDI-TUNNICLIFFE, ALAN; COOPER, ALAN; SMITH, BRIAN O.

BIOSCIENCE REPORTS

PORTLAND PRESS LTD

Año: 2019 vol. 39

0144-8463

Intracellular lipid-binding proteins (iLBPs) of the fatty acid-binding protein (FABP) family ofanimals transport, mainly fatty acids or retinoids, are confined to the cytosol and havehighly similar 3D structures. In contrast, nematodes possess fatty acid-binding proteins(nemFABPs) that are secreted into the perivitelline fluid surrounding their developing embryos.We report structures of As-p18, a nemFABP of the large intestinal roundworm Ascarissuum, with ligand bound, determined using X-ray crystallography and nuclear magnetic resonancespectroscopy. In common with other FABPs, As-p18 comprises a ten β-strand barrelcapped by two short α-helices, with the carboxylate head group of oleate tethered inthe interior of the protein. However, As-p18 exhibits two distinctive longer loops amongstβ-strands not previously seen in a FABP. One of these is adjacent to the presumed ligandentry portal, so it may help to target the protein for efficient loading or unloading of ligand.The second, larger loop is at the opposite end of the molecule and has no equivalent in anyiLBP structure yet determined. As-p18 preferentially binds a single 18-carbon fatty acid ligandin its central cavity but in an orientation that differs from iLBPs. The unusual structuralfeatures of nemFABPs may relate to resourcing of developing embryos of nematodes.