PXD016391

PXD016391 is an original dataset announced via ProteomeXchange.

Title	Structural basis for lipid binding and function by an evolutionally conserved protein, Serum Amyloid A
Description	Serum amyloid A (SAA) is a plasma protein that transports lipids during inflammation. To explore SAA solution conformations and lipid binding mechanism, we used hydrogen-deuterium exchange mass spectrometry, lipoprotein reconstitution, sequence analysis and molecular dynamics simulations. Solution conformations of lipid-bound and lipid-free mSAA1 at pH~7 agreed in details with the crystal structures but also showed important differences. The results revealed that amphipathic α-helices h1 and h3 comprise a lipid-binding site that is partially pre-formed in solution, is stabilized on lipoproteins, and shows lipid-induced folding of h3. This site sequesters apolar ligands via a concave hydrophobic surface in SAA oligomers. The largely disordered C-terminal region is conjectured to mediate promiscuous binding of other ligands. The h1-h2 linker region forms an unexpected β-hairpin that may represent an early amyloidogenic intermediate. The results establish structural underpinnings for understanding SAA interactions with lipids and other ligands, its evolutional conservation, and its transition to amyloid.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:00:12.875.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John R. Engen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-21 15:28:36	ID requested
1	2020-02-17 12:59:08	announced
⏵ 2	2024-10-22 05:00:13	announced	2024-10-22: Updated project metadata.

10.1016/j.jmb.2020.01.029;

Frame NM, Kumanan M, Wales TE, Bandara A, F, ä, ndrich M, Straub JE, Engen JR, Gursky O, Structural Basis for Lipid Binding and Function by an Evolutionarily Conserved Protein, Serum Amyloid A. J Mol Biol, 432(7):1978-1995(2020) [pubmed]

submitter keyword: Hydrogen-deuterium exchange mass spectrometry

molecular dynamics simulations

lipoprotein nanoparticle

intrinsically disordered protein

β-hairpin misfolding intermediate

inflammation and immunity

John R. Engen
contact affiliation	Dept of Chemistry & Chemical Biology, Northeastern University
contact email	j.engen@northeastern.edu
lab head
John R. Engen
contact affiliation	Northeastern University
contact email	j.engen@northeastern.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/2020/02/PXD016391

PRIDE project URI

• PRIDE
  1. PXD016391
     1. Label: PRIDE project
     2. Name: Structural basis for lipid binding and function by an evolutionally conserved protein, Serum Amyloid A