6SVL

human Myeloid-derived growth factor (MYDGF) in complex with neutralizing Fab

Summary for 6SVL

• Entry DOI: 10.2210/pdb6svl/pdb
• Descriptor: Fab_heavy_chain, Fab_light_chain, Myeloid-derived growth factor, ... (5 entities in total)
• Functional Keywords: mydgf, growth factor, cytokine, fab, neutralizing antibody
• Biological source: Homo sapiens; More
• Total number of polymer chains: 18
• Total formula weight: 408575.39

Authors

Ebenhoch, R.,Nar, H. (deposition date: 2019-09-18, release date: 2019-11-27, Last modification date: 2024-01-24)

Primary citation

Ebenhoch, R.,Akhdar, A.,Reboll, M.R.,Korf-Klingebiel, M.,Gupta, P.,Armstrong, J.,Huang, Y.,Frego, L.,Rybina, I.,Miglietta, J.,Pekcec, A.,Wollert, K.C.,Nar, H.
Crystal structure and receptor-interacting residues of MYDGF - a protein mediating ischemic tissue repair.
Nat Commun, 10:5379-5379, 2019

PubMed 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.

PubMed: 31772377
DOI: 10.1038/s41467-019-13343-7

Experimental method

X-RAY DIFFRACTION (1.58 Å)