8SDF

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody CC25.4

PDB DOI: https://doi.org/10.2210/pdb8SDF/pdb

Classification: IMMUNE SYSTEM
Organism(s): Severe acute respiratory syndrome coronavirus 2, Homo sapiens
Expression System: Trichoplusia ni, Homo sapiens
Mutation(s): No

Deposited: 2023-04-06 Released: 2024-03-13
Deposition Author(s): Yuan, M., Wilson, I.A.
Funding Organization(s): National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID), Bill & Melinda Gates Foundation

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.79 Å
R-Value Free: 0.218
R-Value Work: 0.185
R-Value Observed: 0.187

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.

Song, G., Yuan, M., Liu, H., Capozzola, T., Lin, R.N., Torres, J.L., He, W.T., Musharrafieh, R., Dueker, K., Zhou, P., Callaghan, S., Mishra, N., Yong, P., Anzanello, F., Avillion, G., Vo, A.L., Li, X., Makhdoomi, M., Feng, Z., Zhu, X., Peng, L., Nemazee, D., Safonova, Y., Briney, B., Ward, A.B., Burton, D.R., Wilson, I.A., Andrabi, R.

(2023) bioRxiv

PubMed: 37162858 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1101/2023.04.26.538488
Primary Citation of Related Structures:
8SDF, 8SDG, 8SDH

PubMed Abstract:
Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.

Organizational Affiliation

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Macromolecule Content

Total Structure Weight: 143.81 kDa
Atom Count: 10,506
Modelled Residue Count: 1,261
Deposited Residue Count: 1,302
Unique protein chains: 3

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Spike protein S1	A [auth Z], D [auth A]	205	Severe acute respiratory syndrome coronavirus 2	Mutation(s): 0
UniProt
Find proteins for P0DTC2 (Severe acute respiratory syndrome coronavirus 2) Explore P0DTC2 Go to UniProtKB: P0DTC2
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P0DTC2
Glycosylation
Glycosylation Sites: 1	Glycosylation Focus chain A [auth Z] Focus chain D [auth A]	Go to GlyGen: P0DTC2-1
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Neutralizing antibody CC25.4 heavy chain	B [auth H], E [auth B]	229	Homo sapiens	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Neutralizing antibody CC25.4 light chain	C [auth L], F [auth C]	217	Homo sapiens	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose	G [auth D]	3		N-Glycosylation	Interactions Focus chain G [auth D] Interactions & Density Focus chain G [auth D]
Glycosylation Resources
GlyTouCan: G21290RB GlyCosmos: G21290RB GlyGen: G21290RB

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain M [auth A] MOL2 format, chain M [auth A] mmCIF format, chain M [auth A]	M [auth A]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain M [auth A] Interactions & Density Focus chain M [auth A]
MPD Query on MPD Download Ideal Coordinates CCD File SDF format, chain H [auth Z] SDF format, chain I [auth Z] SDF format, chain J [auth H] SDF format, chain K [auth L] SDF format, chain L SDF format, chain N [auth A] SDF format, chain O [auth B] SDF format, chain P [auth C] MOL2 format, chain H [auth Z] MOL2 format, chain I [auth Z] MOL2 format, chain J [auth H] MOL2 format, chain K [auth L] MOL2 format, chain L MOL2 format, chain N [auth A] MOL2 format, chain O [auth B] MOL2 format, chain P [auth C] mmCIF format, chain H [auth Z] mmCIF format, chain I [auth Z] mmCIF format, chain J [auth H] mmCIF format, chain K [auth L] mmCIF format, chain L mmCIF format, chain N [auth A] mmCIF format, chain O [auth B] mmCIF format, chain P [auth C]	H [auth Z] I [auth Z] J [auth H] K [auth L] L H [auth Z], I [auth Z], J [auth H], K [auth L], L, N [auth A], O [auth B], P [auth C]	(4S)-2-METHYL-2,4-PENTANEDIOL C₆ H₁₄ O₂ SVTBMSDMJJWYQN-YFKPBYRVSA-N		Interactions Focus chain H [auth Z] Focus chain I [auth Z] Focus chain J [auth H] Focus chain K [auth L] Focus chain L Focus chain N [auth A] Focus chain O [auth B] Focus chain P [auth C] Interactions & Density Focus chain H [auth Z] Focus chain I [auth Z] Focus chain J [auth H] Focus chain K [auth L] Focus chain L Focus chain N [auth A] Focus chain O [auth B] Focus chain P [auth C]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.79 Å
R-Value Free: 0.218
R-Value Work: 0.185
R-Value Observed: 0.187
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 58.204	α = 90
b = 142.996	β = 94.13
c = 82.928	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
XDS	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2024-03-13

Deposition Author(s):

Yuan, M.

Wilson, I.A.

Funding Organization	Location	Grant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)	United States	R01AI170928
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)	United States	CHAVD UM1 AI44462
Bill & Melinda Gates Foundation	United States	INV-004923