Structural characterization of a novel Fatty Acid Binding Protein from nematodes, As-p18”

MARINA IBÁÑEZ SHIMABUKURO; M. FLORENCIA REY BURUSCO; MALCOLM W. KENNEDY; ALAN COOPER; BETINA CÓRSICO; BRIAN O. SMITH

Snowbird, Utah, USA

Simposio; Keystone Symposia on Molecular and Cellular Biology: Frontiers of NMR in Biology; 2013

As-p18 is a developmentally regulated fatty acid binding protein (FABP) found in the perivitelline fluid surrounding the infective third stage larva (L3) of the parasitic nematode Ascaris suum. Once fully developed, the L3 undergoes developmental arrest, persisting for several years until ingestion by the host, but little is known about the biochemical and physiological basis for such long term survival. One of the most abundant protein components in the fluid that surrounds the developing larva is the FABP, As-p18. The overall structure of As-p18 has been predicted to be very similar to other FABPs. However, phylogenetic analysis revealed that As-p18 together with other nematode proteins comprise a distinct cluster within the FABP family. The tight developmental control of thier expression, their extended sequences and the presence of a leader peptide in the gene sequence –determining that it is secreted– further distinguish these nematode proteins from other FABPs. Detailed structural information could help to explain nemFABPs specific functions, exclusive to nematodes. Here we present the solution structure of As-p18 complexed with oleate and an analysis of the protein-ligand interactions derived from isotope-filtered NMR experiments. Titration experiments showed only one ligand binding site, but the ligand is bound in a different mode than in other FABPs. As-p18 also exhibits an extended loop in an unexpected location, probably found only in these proteins and which may be involved in the nematode-specific functions. This work provides a structural characterisation of As-p18 that may contribute to the understanding of this protein´s rol in A. suum infective eggs, and more generally to the unique features of nematode FABPs. Supported by Welcome Trust Grant 083625