A paper published in Life Science Alliance by the Molinari’s laboratory characterizes TMX5, a member of the protein disulfide isomerase (PDI) family, and reports on the involvement of ERp44, another member of the PDI family, in determining intracellular distribution and clients’ selection of TMX5.
Bellinzona – October 17 2024 – The endoplasmic reticulum (ER) is the organelle of nucleated cells, where proteins are synthesized and folded in their functional shape. Maturation of the several thousand different proteins produced in the ER relies on more than 20 members of the protein disulfide isomerase (PDI) family that regulate the formation of covalent disulfide bonds between cysteine residues that stabilize the proteins’ structure. The PDI family includes five membrane-bound members, TMX1, TMX2, TMX3, TMX4, and TMX5. In previous studies, we characterized the functions of TMX1 that assists conformational maturation and degradation of a subset of cellular proteins, and of TMX4 that regulates the ultrastructure of the nuclear envelope in cells experiencing and recovering from cellular stresses. In our latest publication, we study TMX5, the least-known member of the family. We establish that TMX5 covalently engages via its active site cysteine residue at position 220 a list of clients including single- and multipass Golgi-resident proteins. TMX5 also interacts with the PDI family member ERp44 via a mixed disulfide between its non-catalytic cysteine residues 114 and 124 and the catalytic cysteine residue 29 of ERp44. This modulable interaction determines the localization of TMX5, which lacks conventional ER retention sequences normally found in PDI family members, in pre-Golgi compartments.
