PDBsum entry 3eyo

Immune system

PDB id

3eyo

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Contents

			Protein chains

					213 a.a. *


					212 a.a. *

			Waters ×380

* Residue conservation analysis

PDB id:

3eyo

Links

Name:

Immune system

Title:

Crystal structure of anti-human cytomegalovirus antibody 8f9

Structure:

8f9 fab. Chain: a, c. Engineered: yes. Ad-2. Chain: b, d. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å

R-factor:

0.241

R-free:

0.268

Authors:

C.A.Thomson,S.Bryson,G.R.Mclean,A.L.Creagh,E.F.Pai,J.W.Schrader

Key ref:

C.A.Thomson et al. (2008). Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus. Embo J, 27, 2592-2602. PubMed id: 18772881

Date:

21-Oct-08

Release date:

16-Dec-08

PROCHECK

	Headers

	References

Protein chains

Q6PJF2 (Q6PJF2_HUMAN) - IGK@ protein from Homo sapiens

Seq: Struc:					235 a.a. 213 a.a.*

Protein chains

Q0ZCG9 (Q0ZCG9_HUMAN) - Immunglobulin heavy chain variable region (Fragment) from Homo sapiens

Seq: Struc:					121 a.a. 212 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 52 residue positions (black crosses)

	Embo J 27:2592-2602 (2008)
PubMed id: 18772881

Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.
C.A.Thomson, S.Bryson, G.R.McLean, A.L.Creagh, E.F.Pai, J.W.Schrader.

ABSTRACT

Immunoglobulin genes are generated somatically through specialized mechanisms resulting in a vast repertoire of antigen-binding sites. Despite the stochastic nature of these processes, the V-genes that encode most of the antigen-combining site are under positive evolutionary selection, raising the possibility that V-genes have been selected to encode key structural features of binding sites of protective antibodies against certain pathogens. Human, neutralizing antibodies to human cytomegalovirus that bind the AD-2S1 epitope on its gB envelope protein repeatedly use a pair of well-conserved, germline V-genes IGHV3-30 and IGKV3-11. Here, we present crystallographic, kinetic and thermodynamic analyses of the binding site of such an antibody and that of its primary immunoglobulin ancestor. These show that these germline V-genes encode key side chain contacts with the viral antigen and thereby dictate key structural features of the hypermutated, high-affinity neutralizing antibody. V-genes may thus encode an innate, protective immunological memory that targets vulnerable, invariant sites on multiple pathogens.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20972421

H.Mao, J.J.Graziano, T.M.Chase, C.A.Bentley, O.A.Bazirgan, N.P.Reddy, B.D.Song, and V.V.Smider (2010).
Spatially addressed combinatorial protein libraries for recombinant antibody discovery and optimization.

Nat Biotechnol, 28, 1195-1202.

20147404

J.P.Julien, N.Huarte, R.Maeso, S.G.Taneva, A.Cunningham, J.L.Nieva, and E.F.Pai (2010).
Ablation of the complementarity-determining region H3 apex of the anti-HIV-1 broadly neutralizing antibody 2F5 abrogates neutralizing capacity without affecting core epitope binding.

J Virol, 84, 4136-4147.

20421498

P.Farci, G.Diaz, Z.Chen, S.Govindarajan, A.Tice, L.Agulto, S.Pittaluga, D.Boon, C.Yu, R.E.Engle, M.Haas, R.Simon, R.H.Purcell, and F.Zamboni (2010).
B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure.

Proc Natl Acad Sci U S A, 107, 8766-8771.

20017116

R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.

J Mol Recognit, 23, 1.

20970857

R.Robert, M.P.Lefranc, A.Ghochikyan, M.G.Agadjanyan, D.H.Cribbs, W.E.Van Nostrand, K.L.Wark, and O.Dolezal (2010).
Restricted V gene usage and VH/VL pairing of mouse humoral response against the N-terminal immunodominant epitope of the amyloid β peptide.

Mol Immunol, 48, 59-72.

19063692

D.Kanduc (2009).
Epitopic peptides with low similarity to the host proteome: towards biological therapies without side effects.

Expert Opin Biol Ther, 9, 45-53.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.