20211015 Chang CI paper photo

Complete three-dimensional structures of the Lon protease translocating a protein substrate

Complete three-dimensional structures of the Lon protease translocating a protein substrate

Science Advances. 2021 Oct 15; 7(42):eabj7835. Epub 2021 Oct 15.
doi: 10.1126/sciadv.abj7835

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Li S, Hsieh KY, Kuo CI, Lee SH, Pintilie GD, Zhang K, Chang CI

摘要

Lon is an evolutionarily conserved proteolytic machine carrying out a wide spectrum of biological activities by degrading misfolded damaged proteins and specific cellular substrates. Lon contains a large N-terminal domain and forms a hexameric core of fused adenosine triphosphatase and protease domains. Here, we report two complete structures of Lon engaging a substrate, determined by cryo–electron microscopy to 2.4-angstrom resolution. These structures show a multilayered architecture featuring a tensegrity triangle complex, uniquely constructed by six long N-terminal helices. The interlocked helix triangle is assembled on the top of the hexameric core to spread a web of six globular substrate-binding domains. It serves as a multipurpose platform that controls the access of substrates to the AAA+ ring, provides a ruler-based mechanism for substrate selection, and acts as a pulley device to facilitate unfolding of the translocated substrate. This work provides a complete framework for understanding the structural mechanisms of Lon.