PXD049065

PXD049065 is an original dataset announced via ProteomeXchange.

Title	Structural insights into IMP2 dimerization and RNA binding
Description	IGF2BP2 (IMP2) is an RNA binding protein contributing to tumorigenesis across various cancers as well as to metabolic disorders. With the growing interest in drug discovery efforts targeting IMP2, an understanding of its structural properties and biological behavior are needed. Thus far, only partial structural information was available based on selected domains purification. In this study we used a combination of mass photometry, Hydrogen-Deuterium exchange-mass spectrometry, small angle X-ray scattering, and additional biophysical experiments to investigate the behavior of full-length IMP2 protein in presence or absence or RNA. We found that full-length IMP2 forms multiple oligomeric states and predominantly adopts a dimer conformation. Interestingly, the dimer is formed in a head-to-tail orientation by KH34 and RRM1 domains. In the presence of a known IMP2-binding RNA target, we observed a pseudo-symmetric dimer much different from its RNA unbound state, with the KH12 domains of each IMP2 molecule forming the dimeric interface. Additionally, we observed that IMP2 oligomer species, including dimers and higher-order oligomers, are sensitive to environmental conditions such as ionic strength as well as the presence or absence of RNA. Our results provide the first insight into IMP2 homodimerization, which will provide novel opportunities for disrupting its function towards more effective IMP2 inhibitors.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_16:17:45.281.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Timothy O'Leary
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-31 21:03:10	ID requested
⏵ 1	2026-05-24 16:17:46	announced

Zorc SA, Munoz-Tello P, O'Leary T, Yu X, Karadi Giridhar MN, Hondros AD, Hansel-Harris A, Forli S, Griffin PR, Kojetin DJ, Roy RN, Janiszewska M, Structural insights into IMP2 dimerization and RNA binding. J Struct Biol, 217(4):108247(2025) [pubmed]

10.1016/j.jsb.2025.108247;

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: IMP2, HDX-MS

Patrick R. Griffin
contact affiliation	Professor, Molecular Medicine, Wertheim UF Scripps, USA
contact email	pgriffin2@ufl.edu
lab head
Timothy O'Leary
contact affiliation	The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
contact email	olearytimothy@ufl.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/2026/05/PXD049065

PRIDE project URI

• PRIDE
  1. PXD049065
     1. Label: PRIDE project
     2. Name: Structural insights into IMP2 dimerization and RNA binding