Abstract:
:Tripeptidyl peptidase II (TPP II) is the largest known eukaryotic protease (6 MDa). It is believed to act downstream of the 26S proteasome, cleaving tripeptides from the N termini of longer peptides, and it is implicated in numerous cellular processes. Here we report the structure of Drosophila TPP II determined by a hybrid approach. We solved the structure of the dimer by X-ray crystallography and docked it into the three-dimensional map of the holocomplex, which we obtained by single-particle cryo-electron microscopy. The resulting structure reveals the compartmentalization of the active sites inside a system of chambers and suggests the existence of a molecular ruler determining the size of the cleavage products. Furthermore, the structure suggests a model for activation of TPP II involving the relocation of a flexible loop and a repositioning of the active-site serine, coupling it to holocomplex assembly and active-site sequestration.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Chuang CK,Rockel B,Seyit G,Walian PJ,Schönegge AM,Peters J,Zwart PH,Baumeister W,Jap BKdoi
10.1038/nsmb.1870subject
Has Abstractpub_date
2010-08-01 00:00:00pages
990-6issue
8eissn
1545-9993issn
1545-9985pii
nsmb.1870journal_volume
17pub_type
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