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Title: Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum

Journal Article · · Nature Communications

Human myeloid-derived growth factor (hMYDGF) is a 142-residue protein with a C-terminal endoplasmic reticulum (ER) retention sequence (ERS). Extracellular MYDGF mediates cardiac repair in mice after anoxic injury. Although homologs of hMYDGF are found in eukaryotes as distant as protozoans, its structure and function are unknown. Here we present the NMR solution structure of hMYDGF, which consists of a short α-helix and ten β-strands distributed in three β-sheets. Conserved residues map to the unstructured ERS, loops on the face opposite the ERS, and the surface of a cavity underneath the conserved loops. The only protein or portion of a protein known to have a similar fold is the base domain of VNN1. We suggest, in analogy to the tethering of the VNN1 nitrilase domain to the plasma membrane via its base domain, that MYDGF complexed to the KDEL receptor binds cargo via its conserved residues for transport to the ER.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH); National Science Foundation (NSF)
Grant/Contract Number:
AC05-00OR22725; P01 HL088594; R01 AI125390; P41 GM103399; P41 RR002301; S10 RR002781; S10 RR008438; S10 RR023438; S10 RR025062; S10 RR029220; DMB-8415048; OIA-9977486; BIR-9214394; R01 GM125085; S10 OD018475
OSTI ID:
1649441
Journal Information:
Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

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