PXD056670-1

PXD056670 is an original dataset announced via ProteomeXchange.

Title	Defining the Structural Features of Complement-Active IgM: Surface Ag linker comparison
Description	Immunoglobulin mu (IgM) is a class of mammalian antibodies that are critical for the early stages of adaptive immunity and are the most potent activators of the classical complement cascade. While the relationship between IgM and complement has been appreciated for decades, the structural transitions within IgM upon antigen binding that lead to the activation of the C1 complex remain unresolved. Here we examine the complement activation profiles, binding kinetics, and conformational changes in IgM in different antigen-bound states. Only in the complex with a surface-displayed antigen with multiple Fab arms engaged was the IgM fully capable of driving complement activation. The structural changes within IgM upon antigen binding were monitored by Hydrogen/Deuterium Exchange reveal the predominant structural changes within the Fc core domains upon activation. Collectively, this work establishes key structural and functional qualities that define the complement-active form of IgM.
HostingRepository	PRIDE
AnnounceDate	2025-04-02
AnnouncementXML	Submission_2025-04-02_14:28:09.530.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Charles Mundorff
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	glycosylated residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-09 16:43:05	ID requested
⏵ 1	2025-04-02 14:28:10	announced

10.1016/j.jmb.2025.169104;

Watson MJ, Mundorff CC, Lynch EM, Kollman JM, Kearney JF, Guttman M, Defining the Features of Complement-Active IgM. J Mol Biol, 437(12):169104(2025) [pubmed]

submitter keyword: IgM,HDX-MS, Antibody-antigen interaction

Miklos Guttman
contact affiliation	Department of Medicinal Chemistry, University of Washington
contact email	mguttman@uw.edu
lab head
Charles Mundorff
contact affiliation	University of Washington
contact email	mundorff@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056670
     1. Label: PRIDE project
     2. Name: Defining the Structural Features of Complement-Active IgM: Surface Ag linker comparison