2KGL

NMR solution structure of MESD

Summary for 2KGL

• Entry DOI: 10.2210/pdb2kgl/pdb
• Descriptor: Mesoderm development candidate 2 (1 entity in total)
• Functional Keywords: mesd, lrp5/6, chaperone, ywtd, wnt
• Biological source: Mus musculus (mouse)
• Cellular location: Endoplasmic reticulum: Q9ERE7
• Total number of polymer chains: 1
• Total formula weight: 22074.83

Authors

Chen, J.,Wang, J. (deposition date: 2009-03-12, release date: 2010-03-23, Last modification date: 2024-05-01)

Primary citation

Chen, J.,Liu, C.C.,Li, Q.,Nowak, C.,Bu, G.,Wang, J.
Two Structural and Functional Domains of MESD Required for Proper Folding and Trafficking of LRP5/6.
Structure, 19:313-323, 2011

PubMed Abstract: 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 β-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.

PubMed: 21397183
DOI: 10.1016/j.str.2011.01.010

Experimental method

SOLUTION NMR