PDBsum entry 6svk

Cytokine

PDB id: 6svk

Contents

Protein chains

135 a.a.

Ligands

MLI

Waters ×180

PDB id:

6svk

Name:

Cytokine

Title:

Human myeloid-derived growth factor (mydgf)

Structure:

Myeloid-derived growth factor. Chain: a, b. Synonym: mydgf. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mydgf, c19orf10. Expressed in: homo sapiens. Expression_system_taxid: 9606.

Resolution:

1.60Å R-factor: 0.219 R-free: 0.247

Authors:

R.Ebenhoch,H.Nar

Key ref:

R.Ebenhoch et al. (2019). Crystal structure and receptor-interacting residues of MYDGF - a protein mediating ischemic tissue repair. Nat Commun, 10, 5379. PubMed id: 31772377 DOI: 10.1038/s41467-019-13343-7

Date:

18-Sep-19 Release date: 27-Nov-19

Protein chains

Q969H8  (MYDGF_HUMAN) -  Myeloid-derived growth factor from Homo sapiens

Seq: 173 a.a.

Struc: 135 a.a.

DOI no: 10.1038/s41467-019-13343-7

Nat Commun 10:5379 (2019)

PubMed id: 31772377

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

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.

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.