InterPro domain: IPR019330

LRP chaperone MESD (also known as mesoderm development candidate 2) represents a set of highly conserved proteins found from nematodes to humans. It is a chaperone that specifically assists with the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). It also acts as a modulator of the Wnt pathway, since some LDLRs are coreceptors for the canonical Wnt pathway and is essential for specification of embryonic polarity and mesoderm induction [ 1 ]. The Drosophila homologue, known as boca, is an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members [ 2 ].

The final C-terminal residues, KEDL, are the endoplasmic reticulum retention sequence as it is an ER protein specifically required for the intracellular trafficking of members of the low-density lipoprotein family of receptors (LDLRs) [ 3 ]. The N- and C-terminal sequences are predicted to adopt a random coil conformation, with the exception of an isolated predicted helix within the N-terminal region, The central folded domain flanked by natively unstructured regions is the necessary structure for facilitating maturation of LRP6 (Low-Density Lipoprotein Receptor-Related Protein 6 Maturation) [ 3 ].

1. Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell 112, 355-67
2. Boca, an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members in Drosophila. Cell 112, 343-54
3. Requirement for natively unstructured regions of mesoderm development candidate 2 in promoting low-density lipoprotein receptor-related protein 6 maturation. Biochemistry 46, 6570-7