Structure, Folding and Stability of Nucleoside Diphosphate Kinases

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Nucleoside diphosphate kinases (NDPKs) are essential oligomeric proteins catalyzing nucleoside triphosphate synthesis.
• NDPKs exhibit a conserved ferredoxin fold across diverse organisms and possess independent monomeric activity.
• Monomers assemble into dimers, tetramers, and hexamers, crucial for NDPK function.

Purpose of the Study:

• To review advances in the structure, folding, and stability of NDPKs.
• To explore the structural basis of NDPK oligomerization and its impact on catalytic efficiency.
• To highlight the need for high-resolution structural data of NDPK complexes to understand diverse functions.

Main Methods:

• X-ray crystallography has elucidated the tridimensional structure of NDPK subunits.
• Analysis of conserved ferredoxin fold in prokaryotes, archaea, eukaryotes, and viruses.
• Review of existing literature on NDPK assembly, catalytic mechanisms, and additional functions.

Main Results:

• NDPK monomers are functionally independent but require assembly into dimers, tetramers, or hexamers for activity.
• Oligomeric assembly interfaces vary significantly, yet catalytic efficiency remains largely unaffected.
• Hexamers stabilize the complex and induce catalytic site formation, while the role of tetramers is unclear.

Conclusions:

• Despite varied assembly interfaces, NDPK catalytic efficiency is surprisingly robust.
• Understanding the structural mechanisms behind NDPK's diverse functions, including metastasis and cytoskeleton dynamics, requires further high-resolution structural studies.
• Further research into NDPK structure-function relationships is critical for deciphering its multifaceted roles.