7MK0

Trypanosoma cruzi Nucleoside Diphosphate Kinase 1 form a quinary multihexameric structure

7MK0 の概要

• エントリーDOI: 10.2210/pdb7mk0/pdb
• 分子名称: Nucleoside diphosphate kinase (1 entity in total)
• 機能のキーワード: kinase, cruzi, ndpk1, transferase
• 由来する生物種: Trypanosoma cruzi
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 401812.03

構造登録者

Gomez, J.A.,Aguilar, C.F. (登録日: 2021-04-21, 公開日: 2022-01-12, 最終更新日: 2023-10-18)

主引用文献

Gomez Barroso, J.A.,Miranda, M.R.,Pereira, C.A.,Garratt, R.C.,Aguilar, C.F.
X-ray diffraction and in vivo studies reveal the quinary structure of Trypanosoma cruzi nucleoside diphosphate kinase 1: a novel helical oligomer structure.
Acta Crystallogr D Struct Biol, 78:30-42, 2022

PubMed Abstract: Trypanosoma cruzi is a flagellated protozoan parasite that causes Chagas disease, which represents a serious health problem in the Americas. Nucleoside diphosphate kinases (NDPKs) are key enzymes that are implicated in cellular energy management. TcNDPK1 is the canonical isoform in the T. cruzi parasite. TcNDPK1 has a cytosolic, perinuclear and nuclear distribution. It is also found in non-membrane-bound filaments adjacent to the nucleus. In the present work, X-ray diffraction and in vivo studies of TcNDPK1 are described. The structure reveals a novel, multi-hexameric, left-handed helical oligomer structure. The results of directed mutagenesis studies led to the conclusion that the microscopic TcNDPK1 granules observed in vivo in T. cruzi parasites are made up by the association of TcNDPK1 oligomers. In the absence of experimental data, analysis of the interactions in the X-ray structure of the TcNDPK1 oligomer suggests the probable assembly and disassembly steps: dimerization, assembly of the hexamer as a trimer of dimers, hexamer association to generate the left-handed helical oligomer structure and finally oligomer association in a parallel manner to form the microscopic TcNDPK1 filaments that are observed in vivo in T. cruzi parasites. Oligomer disassembly takes place on the binding of substrate in the active site of TcNDPK1, leading to dissociation of the hexamers. This study constitutes the first report of such a protein arrangement, which has never previously been seen for any protein or NDPK. Further studies are needed to determine its physiological role. However, it may suggest a paradigm for protein storage reflecting the complex mechanism of action of TcNDPK1.

PubMed: 34981759
DOI: 10.1107/S2059798321011219

実験手法

X-RAY DIFFRACTION (3.5 Å)