1mkc

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C-TERMINAL DOMAIN OF MIDKINE

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Midkine (MK) is a 13 kDa heparin-binding polypeptide which enhances, neurite outgrowth, neuronal cell survival and plasminogen activator, activity. MK is structurally divided into two domains, and most of the, biological activities are located on the C-terminal domain. The solution, structures of the two domains were determined by NMR. Both domains consist, of three antiparallel beta-strands, but the C-terminal domain has a long, flexible hairpin loop where a heparin-binding consensus sequence is, located. Basic residues on the beta-sheet of the C-terminal domain form, another heparin-binding site. Measurement of NMR signals in the presence, of a heparin oligosaccharides verified that multiple amino acids in the, two sites participated in heparin binding. The MK dimer has been shown to, be the active form, giving signals to endothelial cells and probably to, neuronal cells. We present a head-to-head dimer model of MK. The model was, supported by the results of cross-linking experiments using, transglutaminase. The dimer has a fused heparin-binding site at the dimer, interface of the C-terminal domain, and the heparin-binding sites on MK, fit the sulfate group clusters on heparin. These features are consistent, with the proposed stronger heparin-binding activity and biological, activity of the dimer.

Disease

Known disease associated with this structure: Mesomelic dysplasia, Kantaputra type OMIM:[156232]

About this Structure

1MKC is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

Solution structure of midkine, a new heparin-binding growth factor., Iwasaki W, Nagata K, Hatanaka H, Inui T, Kimura T, Muramatsu T, Yoshida K, Tasumi M, Inagaki F, EMBO J. 1997 Dec 1;16(23):6936-46. PMID:9384573

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