PXD059974-1

PXD059974 is an original dataset announced via ProteomeXchange.

Title	Elucidating PTEN Conformational Dynamics and Phosphatase Regulation via Integrative Modeling and Mutation Prediction
Description	PTEN (Phosphatase and TENsin homolog deleted on chromosome ten) is a major tumor suppressor gene that is frequently mutated or lost under cancerous conditions. PTEN is a dual-specificity phosphatase that negatively regulates the PI3K/AKT/mTOR signaling pathway at the plasma membrane (PM). Its functional regulation and cellular localization are known to be conformationally driven. Access to the PM is phospho-regulated by open and closed PTEN forms. However, clarifying the underlying structural mechanisms is still an open avenue of research. Here, we apply an integrative structural modeling approach, combining coarse-grained and all-atom molecular dynamics with experimental crosslinking mass spectrometry. Conformational exchange between an “eased” form and a “strained” form brings the protein’s phosphatase and C2 domains closer together, blocking the catalytic site, and affecting the loops involved in PM binding. Our full-length PTEN models, AlphaMissense, and RaSP were used to better predict the consequences of PTEN mutations.
HostingRepository	PRIDE
AnnounceDate	2025-06-09
AnnouncementXML	Submission_2025-06-09_10:09:09.956.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059974
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Belinda Willard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-20 05:49:31	ID requested
⏵ 1	2025-06-09 10:09:10	announced

10.6019/PXD059974;

submitter keyword: molecular dynamics, molecular modeling, molecular biology, conformational change, RaSP stability prediction, crosslinking mass spectrometry (XL-MS), AlphaMissense, clinical mutation, integrative structural modeling,Phosphatase and tensin homolog (PTEN)

Jennifer Erin Dawson
contact affiliation	Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, United States.
contact email	DAWSONJ8@ccf.org
lab head
Belinda Willard
contact affiliation	Cleveland Clinic
contact email	willarb@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059974
     1. Label: PRIDE project
     2. Name: Elucidating PTEN Conformational Dynamics and Phosphatase Regulation via Integrative Modeling and Mutation Prediction