Title

Nucleotide-dependent self-assembly of Nucleoside Diphosphate Kinase (NDPK) in vitro.

Date of Original Version

12-1-2008

Type

Article

PubMed ID

18725328

Abstract or Description

In addition to their role in nucleotide homeostasis, members of the Nucleoside Diphosphate Kinase (NDPK) family have been implicated in tumor metastasis, cell migration and vesicle trafficking. Although its role in most cases depends on nucleotide catalysis, a precise understanding of how the catalytic activity of NDPK supports its function in diverse processes is lacking. Here we report that wild type, but not catalytically inactive (H118C) NDPKB, undergoes dynamic self-assembly into ordered 20-25 nm diameter filaments in vitro. Self-assembly is nucleoside triphosphate dependent, GTP being most effective at promoting polymer formation. In addition, polymerization appears to depend on formation of the phosphoryl-Histidine intermediate of the enzyme, suggesting a previously unappreciated conformational change in NDPK during its catalytic cycle. We hypothesize that the observed nucleotide-dependent self-assembly property of NDPKB may reflect a key feature of NDPK enzymes that enables their function in diverse processes.

DOI

10.1016/j.bbapap.2008.07.011

 

Published In

Biochimica et biophysica acta, 1784, 12, 2045-2051.