PXD072665-1

PXD072665 is an original dataset announced via ProteomeXchange.

Title	Revisiting p53:Sirt1 interaction in the light of controlling p53 acetylation levels
Description	The NAD⁺-dependent deacetylase sirtuin 1 (Sirt1) is known to regulate the tumor suppressor p53 via deacetylation, but the structural basis of the protein-protein interaction between full-length Sirt1 and p53 has so far remained elusive. We apply an integrated approach, combining structural mass spectrometry (MS) with data-driven molecular docking to study the interaction between human p53 and Sirt1. Sirt1 was found to bind exclusively to acetylated p53, forming complexes occurs with a 1:1 stoichiometry, irrespectively of p53’s oligomeric state. The lysine residue at position 582 (K582) in p53 was identified as predominant acetylation site, showing a selective Sirt1-dependent deacetylation at this position. Cross-linking mass spectrometry (XL-MS) provided valuable distance constraints between p53 and Sirt1. Specifically, cross-links created between p53-K382 / Sirt1-K427 and p53-K120 / Sirt1-K622 give hints on a highly flexible interface. Molecular docking was conducted based on the XL-MS distance constraints, positioning Sirt1 at the DNA-binding and tetramerization domains of p53. This gives a rationale for a steric exclusion of additional Sirt1 molecules binding to p53. We present the first structural model of the full-length p53:Sirt1 (1:1) complex, establishing a mechanistic framework that links p53 activity to its Sirt1-controlled acetylation status.
HostingRepository	PRIDE
AnnounceDate	2026-09-09
AnnouncementXML	Submission_2026-09-09_05:41:11.121.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Ihling
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue
Instrument	timsTOF Pro; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-05 11:44:35	ID requested
⏵ 1	2026-09-09 05:41:12	announced

Pandey V, Hause F, Iacobucci C, Ihling CH, Tueting C, Kastritis PL, Arlt C, Sinz A, Revisiting the p53:Sirt1 interaction in light of controlling p53 acetylation levels. Commun Chem, 9(1):(2026) [pubmed]

10.1038/s42004-026-02127-y;

submitter keyword: sirtuin 1, cross-linking, mass spectrometry,p53

Andrea Sinz
contact affiliation	MLU Halle-Wittenberg Inst. f. Pharmacy, Center f. Structural Mass Spectrometry
contact email	andrea.sinz@pharmazie.uni-halle.de
lab head
Christian Ihling
contact affiliation	MLU Halle, Inst. f. Pharmacy
contact email	christian.ihling@pharmazie.uni-halle.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072665
     1. Label: PRIDE project
     2. Name: Revisiting p53:Sirt1 interaction in the light of controlling p53 acetylation levels