Figure 1. Four levels of structure–function relationships.

For each level, labels ‘X’ and ‘Y’ (in red) highlight the interacting entites, namely: (I) amino acid residues, (II) protein domains, (III) well-mixed compartments, bound by phospholipid membrane, bearing PIN modules, and (IV) PINs contained by whole pFTUs. Left: protein domain architecture diagrams, in the style of Bateman & Chothia, 1995 and Fig. 3, illustrating amino acid interaction for both backbone and side-chains. The two identical immunoglobulin superfamily domains shown in level II are a duplication of the one in level I. Right: level III shows schematic bisection of a pFTU bearing two cells: X, an endothelial cell and Y, a hypoblast. The PIN diagram represents the secretion (dashed red arrow) of paracrine FGF from a hypoblast cell to interact with receptors on either cell type within the same pFTU. Level IV depicts the transit of endocrine FGF (e.g. FGF15 or FGF23, Itoh, 2010) from one part of a sFTU to another via an advective system, which is also part of the same sFTU. The advective tubing is diagrammatically positioned between the two pFTUs (labelled X and Y). In this case, the dashed red arrow represents the transition of the FGF hormone either entering (right) or leaving (left) plasma.