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

Valeriu Bortnov, Marco Tonelli, Woonghee Lee, Ziqing Lin, Douglas S. Annis, Omar N. Demerdash, Alex Bateman, Julie C. Mitchell, Ying Ge, John L. Markley, Deane F. Mosher

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish
Article number5612
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

Fingerprint

Dive into the research topics of 'Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum'. Together they form a unique fingerprint.

Cite this