6U9U

Structure of GM9_TH8seq732127 FAB


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses.

Phad, G.E.Pushparaj, P.Tran, K.Dubrovskaya, V.Adori, M.Martinez-Murillo, P.Vazquez Bernat, N.Singh, S.Dionne, G.O'Dell, S.Bhullar, K.Narang, S.Sorini, C.Villablanca, E.J.Sundling, C.Murrell, B.Mascola, J.R.Shapiro, L.Pancera, M.Martin, M.Corcoran, M.Wyatt, R.T.Karlsson Hedestam, G.B.

(2020) J Exp Med 217

  • DOI: https://doi.org/10.1084/jem.20191155
  • Primary Citation of Related Structures:  
    6U3Z, 6U9U

  • PubMed Abstract: 

    Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRs), especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages.


  • Organizational Affiliation

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GM9_TH8seq732127 FAB heavy chainA [auth H]224Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
GM9_TH8seq732127 FAB light chainB [auth L]214Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
F [auth H],
L
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
FMT
Query on FMT

Download Ideal Coordinates CCD File 
E [auth H],
K [auth L]
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
C [auth H]
D [auth H]
G [auth L]
H [auth L]
I [auth L]
C [auth H],
D [auth H],
G [auth L],
H [auth L],
I [auth L],
J [auth L]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 147.709α = 90
b = 147.709β = 90
c = 63.2γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)United StatesP01 AI104722

Revision History  (Full details and data files)

  • Version 1.0: 2019-11-06
    Type: Initial release
  • Version 1.1: 2019-11-20
    Changes: Database references
  • Version 1.2: 2019-12-18
    Changes: Author supporting evidence
  • Version 1.3: 2019-12-25
    Changes: Database references