PDBsum entry 4k3e

Immune system

PDB id: 4k3e

Contents

Protein chains

262 a.a.

216 a.a.

Ligands

TLA

Waters ×507

PDB id:

4k3e

Name:

Immune system

Title:

Crystal structure of bovine antibody blv5b8 with ultralong cdr h3

Structure:

Bovine antibody with ultralong cdr h3, heavy chain. Chain: h, i. Engineered: yes. Bovine antibody with ultralong cdr h3, light chain. Chain: l, m. Synonym: igl@ protein. Engineered: yes

Source:

Bos taurus. Bovine. Organism_taxid: 9913. Gene: igh. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Gene: igl, igl@.

Resolution:

2.20Å R-factor: 0.204 R-free: 0.240

Authors:

D.C.Ekiert,F.Wang,I.A.Wilson

Key ref:

F.Wang et al. (2013). Reshaping antibody diversity. Cell, 153, 1379-1393. PubMed id: 23746848 DOI: 10.1016/j.cell.2013.04.049

Date:

10-Apr-13 Release date: 19-Jun-13

Protein chains

No UniProt id for this chain

Struc: 262 a.a.

Protein chains

Q3T101  (Q3T101_BOVIN) -  IGL@ protein from Bos taurus

Seq: 235 a.a.

Struc: 216 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1016/j.cell.2013.04.049

Cell 153:1379-1393 (2013)

PubMed id: 23746848

Reshaping antibody diversity.

F.Wang, D.C.Ekiert, I.Ahmad, W.Yu, Y.Zhang, O.Bazirgan, A.Torkamani, T.Raudsepp, W.Mwangi, M.F.Criscitiello, I.A.Wilson, P.G.Schultz, V.V.Smider.

ABSTRACT

Some species mount a robust antibody response despite having limited genome-encoded combinatorial diversity potential. Cows are unusual in having exceptionally long CDR H3 loops and few V regions, but the mechanism for creating diversity is not understood. Deep sequencing reveals that ultralong CDR H3s contain a remarkable complexity of cysteines, suggesting that disulfide-bonded minidomains may arise during repertoire development. Indeed, crystal structures of two cow antibodies reveal that these CDR H3s form a very unusual architecture composed of a β strand "stalk" that supports a structurally diverse, disulfide-bonded "knob" domain. Diversity arises from somatic hypermutation of an ultralong DH with a severe codon bias toward mutation to cysteine. These unusual antibodies can be elicited to recognize defined antigens through the knob domain. Thus, the bovine immune system produces an antibody repertoire composed of ultralong CDR H3s that fold into a diversity of minidomains generated through combinations of somatically generated disulfides.