Chaperones: nanomachines that transport and modify other proteins by stretching and colliding

The Hsp70 chaperones are proteins involved in many cell processes, including quality control of other proteins, their modification and transport through membranes. So far, three possible mechanisms of operation had been suggested for these molecular nanomachines (one passive, another active, and an intermediate termed "entropic pulling"), but the correct model was not known.

A paper published in the journal Nature Structural and Molecular Biology shows that Hsp70 chaperones carry out their functions through collisions and stretching. These observations fit best with the mechanism of the proposed "entropic pulling" model.

The work was conducted by scientists at the Centro Nacional de BIotecnología of the CSIC (CNB-CSIC) in collaboration with the Center for Health Sciences at the University of Texas (San Antonio, TX, USA) and the National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD, USA).

The study identifies the mechanism used by Hsp70 to remove the cages coated with clathrin -a protein that lines the interior of vesicles responsible for introducing materials into the cell.

The secret of Hsp70’s strength

"Hsp70 molecules bind to the clathrin wall at one end of this protein,” explain José María Valpuesta and Jorge Cuellar, two of the study's authors and CNB-CSIC researchers. “This way, it is free to move by pressing on the wall until the clathrin molecules are dislodged and the cage is dismantled."

This effect on clathrin cages is even more efficient due to the special property of this chaperone to self-associate and form oligomers that produce even greater pressure on the cage walls. "Through this mechanism, they exert the force needed to disassemble the cages," the scientists explain.

The authors of the study say that this mechanism can be generalized to other Hsp70 functions such as protein transport through the membrane of mitochondria, lysosomes or the endoplasmic reticulum.

Rui Sousa, Hsien-Shun Liao, Jorge Cuéllar, Suping Jin, Jose M. Valpuesta, Albert J. Jin and Eileen M. Lafer. Clathrin Coat Disassembly Illuminates the Mechanisms of Hsp70 Force Generation. Nature Structural and Molecular Biology 2016 August 1. doi: 10.1038/nsmb.3272

Photo: Cross section of a clathrin cage (interior blue, exterior yellow/orange) Jose María Valpuesta, Nature Structural and Molecular Biology