Gene

Cell biology

Ecology

Biology

Cytosol

Biochemistry

Ubiquitin

Substrate (aquarium)

Chromosomal translocation

AAA proteins

Enzyme

Conformational change

Chemistry

Proteasome

Deubiquitinating enzyme

Biophysics

Adenosine triphosphate

Hydrolase

ATP hydrolysis

ATPase

Science

Molecular-motor coordination The proteasome is a cytosolic molecular machine that recognizes and degrades unneeded or damaged proteins that have been tagged with ubiquitin. A heterohexameric adenosine triphosphatase motor pulls the substrate into the proteolytic chamber, while at the same time, a protein located at the entrance of this motor removes the ubiquitin. De la Peña et al. trapped the substrate inside the motor by inhibiting removal of ubiquitin. This allowed them to determine cryo–electron microscopy structures in the presence of substrate and adenosine triphosphate (ATP). The findings distinguish three sequential conformational states that show how ATP binding, hydrolysis, and phosphate release are coordinated between the six subunits of the motor to cause the conformational changes that translocate the substrate through the proteasome. Science , this issue p. eaav0725

Substrate-engaged 26<i>S</i> proteasome structures reveal mechanisms for ATP-hydrolysis–driven translocation

Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis–driven translocation