Structural basis for coupled ATP-driven electron transfer in the double-cubane cluster protein

Area of Science:

• Biochemistry
• Structural Biology
• Bioinorganic Chemistry

Background:

• Metalloenzymes utilize ATP-driven electron transfer for reductions at highly negative potentials.
• The double-cubane cluster protein (DCCP) and its reductase (DCCP-R) system facilitates small molecule reductions, but the mechanism of ATP-driven electron transfer remains unclear.

Purpose of the Study:

• To elucidate the structural basis of ATP-driven electron transfer in the DCCP:DCCP-R complex.
• To understand how electrons are channeled from ATP hydrolysis to catalytic sites.

Main Methods:

• X-ray crystallography was used to determine the structures of the DCCP:DCCP-R complex in three distinct states.
• Analysis of protein-protein interactions and cofactor positioning within the complex.

Main Results:

• The DCCP-R homodimer is bridged by a [4Fe4S] cluster, positioned to transfer electrons to both DCCP double-cubane clusters.
• Stable complex formation occurs regardless of oxidation state or nucleotide presence; ATP hydrolysis is essential for electron transfer.
• Hydrogen bond networks link the ATP binding site, the [4Fe4S] cluster, and the DCCP double-cubane cluster, facilitating conformational changes.

Conclusions:

• The study reveals a detailed structural mechanism for ATP-driven electron transfer mediated by an iron-sulfur cluster in the DCCP:DCCP-R system.
• Convergent evolution is suggested by similarities to nitrogenases, indicating a common strategy for ATP-driven electron transfer between iron-sulfur clusters.