| First Author | Chen J | Year | 2011 |
| Journal | Structure | Volume | 19 |
| Issue | 3 | Pages | 313-23 |
| PubMed ID | 21397183 | Mgi Jnum | J:175504 |
| Mgi Id | MGI:5285813 | Doi | 10.1016/j.str.2011.01.010 |
| Citation | Chen J, et al. (2011) Two structural and functional domains of MESD required for proper folding and trafficking of LRP5/6. Structure 19(3):313-23 |
| abstractText | How the endoplasmic reticulum (ER) folding machinery coordinates general and specialized chaperones during protein translation and folding remains an important unanswered question. Here, we show two structural domains in MESD, a specialized chaperone for LRP5/6, carry out dual functions. The chaperone domain forms a complex with the immature receptor, maintaining the beta-propeller (BP) domain in an interaction competent state for epidermal growth factor-repeat binding. This promotes proper folding of the BP domain, causing a binding switch from the chaperone domain to the escort domain. The escort complex ensures LRP5/6 safe-trafficking from the ER to the Golgi by preventing premature ligand-binding. Inside the Golgi, the BP domain may contain a histidine switch, regulating MESD dissociation and retrieval. Together, we generate a plausible cell biology picture of the MESD/LRP5/6 pathway, suggesting that it is the specialized chaperones, MESD, that serves as the folding template to drive proper folding and safe trafficking of large multidomain proteins LRP5/6. |
