PXD011494-1

PXD011494 is an original dataset announced via ProteomeXchange.

Title	Recombinant HIV-1 426c Env Tryptic Digest Glycan Identifications and Semi-Quantification
Description	VRC01-class broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4BS) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env) and are of major interest for vaccine design. Unlike mature antibodies, corresponding VRC01-class germline precursors poorly bind to Env due to their weak ability to overcome the steric hindrance imparted by the glycans surrounding the CD4 BS. To date, immunogen design initiatives have largely relied on removal of these glycans and have met limited success in eliciting VRC01-class bnAbs. To understand elicitation of such bnAbs in humans, we structurally characterized the inferred germline precursor of VRC01 in complex with wild-type core gp120 by X-ray crystallography and modified trimeric 426c Env constructs by single-particle electron microscopy. We then validated glycan length and composition of germline VRC01-compatible Env constructs by EThcD LC-MS/MS. Our results reveal that engagement of the VRC01 germline antibody by a wild-type 426c gp120 is possible and can be enhanced by tailoring glycan length in the vicinity of the CD4BS.
HostingRepository	PRIDE
AnnounceDate	2018-11-21
AnnouncementXML	Submission_2018-11-21_03:42:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Borst
SpeciesList	scientific name: Human immunodeficiency virus 1; NCBI TaxID: 11676;
ModificationList	2-pyrrolidone-5-carboxylic acid (Glu); 2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; iodoacetic acid derivatized residue; complex glycosylation; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-29 03:14:11	ID requested
⏵ 1	2018-11-21 03:42:13	announced

Borst AJ, Weidle CE, Gray MD, Frenz B, Snijder J, Joyce MG, Georgiev IS, Stewart-Jones GB, Kwong PD, McGuire AT, DiMaio F, Stamatatos L, Pancera M, Veesler D, Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core. Elife, 7():(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: VRC01, VRC01GL, GLVRC01, HIV, Human Immunodeficiency Virus, HIV-1, 426c, gp120, Vaccine, Immunogen, Glycan, Oligosaccharide, EndoH, Mannose, CryoEM, Xray Crystallography

David Veesler
contact affiliation	Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
contact email	dveesler@uw.edu
lab head
Andrew Borst
contact affiliation	University of Washington
contact email	borsta2@uw.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/2018/11/PXD011494

PRIDE project URI

• PRIDE
  1. PXD011494
     1. Label: PRIDE project
     2. Name: Recombinant HIV-1 426c Env Tryptic Digest Glycan Identifications and Semi-Quantification