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Crystal structure and receptor-interacting residues of MYDGF - a protein mediating ischemic tissue repair.

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Ebenhoch R, Akhdar A, Reboll MR, Korf-Klingebiel M, Gupta P, Armstrong J, Huang Y, Frego L, Rybina I, Miglietta J, Pekcec A, Wollert KC, Nar H
OpenAccess logo Nat Commun 10 5379 (2019)
Cited: 12 times
EuropePMC logo PMID: 31772377

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.

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  1. Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing. Kober DL, Radhakrishnan A, Goldstein JL, Brown MS, Clark LD, Bai XC, Rosenbaum DM. Cell 184 3689-3701.e22 (2021)
  2. Crystal structure and receptor-interacting residues of MYDGF - a protein mediating ischemic tissue repair. Ebenhoch R, Akhdar A, Reboll MR, Korf-Klingebiel M, Gupta P, Armstrong J, Huang Y, Frego L, Rybina I, Miglietta J, Pekcec A, Wollert KC, Nar H. Nat Commun 10 5379 (2019)


Reviews citing this publication (2)

  1. Myeloid-derived growth factor in diseases: structure, function and mechanisms. Chen P, Huang X, Li W, Wen W, Cao Y, Li J, Huang Y, Hu Y. Mol Med 30 103 (2024)
  2. Proteomic Profile of Endometrial Cancer: A Scoping Review. Serambeque B, Mestre C, Hundarova K, Marto CM, Oliveiros B, Gomes AR, Teixo R, Carvalho AS, Botelho MF, Matthiesen R, Carvalho MJ, Laranjo M. Biology (Basel) 13 584 (2024)

Articles citing this publication (8)



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