PDBsum entry 6svk

Cytokine

PDB id: 6svk

Contents

Protein chains

135 a.a.

Ligands

MLI

Waters ×180

References listed in PDB file

Key reference

• Title: Crystal structure and receptor-Interacting residues of mydgf - A protein mediating ischemic tissue repair.
• Authors: R.Ebenhoch, A.Akhdar, M.R.Reboll, M.Korf-Klingebiel, P.Gupta, J.Armstrong, Y.Huang, L.Frego, I.Rybina, J.Miglietta, A.Pekcec, K.C.Wollert, H.Nar.
• Ref.: Nat Commun, 2019, 10, 5379. [DOI no: 10.1038/s41467-019-13343-7]
• PubMed id: 31772377

Note: In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above have been manually determined.

Abstract

Myeloid-derived growth factor (MYDGF) is a paracrine-acting protein that is produced by bone marrow-derived monocytes and macrophages to protect and repair the heart after myocardial infarction (MI). This effect can be used for the development of protein-based therapies for ischemic tissue repair, also beyond the sole application in heart tissue. Here, we report the X-ray structure of MYDGF and identify its functionally relevant receptor binding epitope. MYDGF consists of a 10-stranded β-sandwich with a folding topology showing no similarities to other cytokines or growth factors. By characterizing the epitope of a neutralizing antibody and utilizing functional assays to study the activity of surface patch-mutations, we were able to localize the receptor interaction interface to a region around two surface tyrosine residues 71 and 73 and an adjacent prominent loop structure of residues 97-101. These findings enable structure-guided protein engineering to develop modified MYDGF variants with potentially improved properties for clinical use.