PXD029542

PXD029542 is an original dataset announced via ProteomeXchange.

Title	Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition
Description	Presequence protease (PreP) degrades presequence peptides cleaved off from nuclear-encoded proteins and other aggregation-prone peptides, such as amyloid β (Aβ). PreP structures have only been determined in a closed conformation; thus, the mechanisms of substrate binding and selectivity remain elusive. Here, we leverage advanced vitrification techniques to overcome the preferential denaturation of one of two ~55 kDa homologous domains of PreP caused by air water interface adsorption, and thereby elucidate cryoEM structures of three apo-PreP open states along with Aβ- and citrate synthase presequence-bound PreP. Together with integrative biophysical and pharmacological approaches, these structures reveal the key stages of the PreP catalytic cycle and how the binding of substrates or PreP inhibitor drives the rigid body motion of the protein for substrate binding and catalysis. Together, our studies provide key mechanistic insights into M16C metalloproteases for future therapeutic innovations.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-21_00:47:14.026.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029542
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sheng Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-03 03:59:04	ID requested
⏵ 1	2022-05-21 00:47:14	announced

Liang WG, Wijaya J, Wei H, Noble AJ, Mancl JM, Mo S, Lee D, Lin King JV, Pan M, Liu C, Koehler CM, Zhao M, Potter CS, Carragher B, Li S, Tang WJ, Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition. Nat Commun, 13(1):1833(2022) [pubmed]

submitter keyword: Presequence protease, Amyloid peptide, cryoEM, HDXMS

Sheng Li
contact affiliation	Department of Medicine, UCSD
contact email	s4li@ucsd.edu
lab head
Sheng Li
contact affiliation	University of California, San Diego
contact email	s4li@ucsd.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/05/PXD029542

PRIDE project URI

• PRIDE
  1. PXD029542
     1. Label: PRIDE project
     2. Name: Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition