P-domain of calnexin/calreticulin superfamily

The type-I integral membrane protein calnexin (CNX) and its soluble paralog calreticulin (CRT) are members of a family of molecular chaperones that function in the endoplasmic reticulum (ER) of eukaryotic cells. These calcium-binding proteins are lectins that bind newly synthesised N-linked glycoproteins to help promote efficient folding and oligomeric assembly. The chaperones act to retain the glycoproteins in the ER while they are still incompletely folded, ensuring that the ER quality control machinery can dispose of misfolded glycoproteins. The family of molecular chaperones are conserved among plants, fungi, and animals.

The P domain contains a high-affinity calcium-binding site and is thought to be involved in either substrate binding or protein-protein interactions. The P domain forms part of the lumenal region in CNX. In both CRT and CNX the P domain forms a protrusion, or arm, extending from the core protein. The amino acid sequence of the P domain is highly conserved and is characteristic for this family of lectins. The structure of the P domain consists of a non-globular proline-rich hairpin fold. The P domain is composed of multiple copies of two types of proline-rich repeat sequences, a 17 amino acid type 1 motif and a 14 amino acid type 2 motif, with the arrangement 111222 in CRT and 11112222 in CNX [11248044, 11583625].