Fig. 1. Schematic diagram depicting the modular structure of megalin. Megalin (LRP-2) is a large, 600 kDa integral membrane protein belonging to the LDL receptor gene family [for a review of the LDL receptor gene family see (Nykjaer and Willnow, 2002; Strickland et al., 2002)]. Its cytoplasmic domain contains PxxP, NPxY, YxxM and LL elements that are thought to be involved in the endocytosis and signaling activities of the receptor. Numerous adaptor molecules have been shown to interact with the megalin cytoplasmic domain including proteins with PTB, PDZ domains as well as ones with ankyrin and tetratrico repeat elements (Gotthardt et al., 2000; Petersen et al., 2003; Rader et al., 2000). The ectodomain of megalin comprises several distinct domains or sequence motifs including ligand-binding-type cysteine-rich repeats (complement-like), epidermal growth factor type cysteine-rich repeats and YWTD domains [each group of six YWTD repeats folds into a beta-propeller structure (Springer, 1998)].

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