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

Abstract

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.

Authors:
ORCiD logo [1];  [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [2];  [3]; ORCiD logo [2]; ORCiD logo [1];  [1];  [1]
  1. Univ. of Wisconsin, Madison, WI (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  3. European Bioinformatics Institute (EMBL-EBI), Hinxton (United Kingdom)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); National Science Foundation (NSF)
OSTI Identifier:
1649441
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
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Proteins; Solution-state NMR

Citation Formats

Bortnov, Valeriu, Tonelli, Marco, Lee, Woonghee, Lin, Ziqing, Annis, Douglas S., Demerdash, Omar N., Bateman, Alex, Mitchell, Julie C., Ge, Ying, Markley, John L., and Mosher, Deane F. Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum. United States: N. p., 2019. Web. https://doi.org/10.1038/s41467-019-13577-5.
Bortnov, Valeriu, Tonelli, Marco, Lee, Woonghee, Lin, Ziqing, Annis, Douglas S., Demerdash, Omar N., Bateman, Alex, Mitchell, Julie C., Ge, Ying, Markley, John L., & Mosher, Deane F. Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum. United States. https://doi.org/10.1038/s41467-019-13577-5
Bortnov, Valeriu, Tonelli, Marco, Lee, Woonghee, Lin, Ziqing, Annis, Douglas S., Demerdash, Omar N., Bateman, Alex, Mitchell, Julie C., Ge, Ying, Markley, John L., and Mosher, Deane F. Mon . "Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum". United States. https://doi.org/10.1038/s41467-019-13577-5. https://www.osti.gov/servlets/purl/1649441.
@article{osti_1649441,
title = {Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum},
author = {Bortnov, Valeriu and Tonelli, Marco and Lee, Woonghee and Lin, Ziqing and Annis, Douglas S. and Demerdash, Omar N. and Bateman, Alex and Mitchell, Julie C. and Ge, Ying and Markley, John L. and Mosher, Deane F.},
abstractNote = {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.},
doi = {10.1038/s41467-019-13577-5},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United States},
year = {2019},
month = {12}
}

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