PDBsum entry 4llm

Immune system

PDB id: 4llm

Contents

Protein chains

101 a.a.

101 a.a.

Waters ×139

PDB id:

4llm

Name:

Immune system

Title:

Structure of redesigned igg1 first constant and lambda domains (ch1:clambda constant redesign 1, crd1) at 1.75a

Structure:

Ig gamma-1 chain c region. Chain: a. Engineered: yes. Mutation: yes. Ig lambda-2 chain c region. Chain: b. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ighg1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: iglc2. Expression_system_taxid: 562

Resolution:

1.75Å R-factor: 0.179 R-free: 0.220

Authors:

A.Pustilnik,S.M.Lewis,X.Wu,A.Sereno,F.Huang,G.Guntas,A.Leaver-Fay, E.M.Smith,C.Ho,C.Hansen-Estruch,A.K.Chamberlain,S.M.Truhlar, B.Kuhlman,S.J.Demarest,S.Atwell

Key ref:

S.M.Lewis et al. (2014). Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat Biotechnol, 32, 191-198. PubMed id: 24463572 DOI: 10.1038/nbt.2797

Date:

09-Jul-13 Release date: 29-Jan-14

Protein chain

P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens

Seq: 399 a.a.

Struc: 101 a.a.*

Protein chain

P0DOY2  (IGLC2_HUMAN) -  Immunoglobulin lambda constant 2 from Homo sapiens

Seq: 106 a.a.

Struc: 101 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1038/nbt.2797

Nat Biotechnol 32:191-198 (2014)

PubMed id: 24463572

Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface.

S.M.Lewis, X.Wu, A.Pustilnik, A.Sereno, F.Huang, H.L.Rick, G.Guntas, A.Leaver-Fay, E.M.Smith, C.Ho, C.Hansen-Estruch, A.K.Chamberlain, S.M.Truhlar, E.M.Conner, S.Atwell, B.Kuhlman, S.J.Demarest.

ABSTRACT

Robust generation of IgG bispecific antibodies has been a long-standing challenge. Existing methods require extensive engineering of each individual antibody, discovery of common light chains, or complex and laborious biochemical processing. Here we combine computational and rational design approaches with experimental structural validation to generate antibody heavy and light chains with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating these interfaces, when simultaneously co-expressed, assemble into bispecific IgG with improved heavy chain-light chain pairing. Bispecific IgGs generated with this approach exhibit pharmacokinetic and other desirable properties of native IgG, but bind target antigens monovalently. As such, these bispecific reagents may be useful in many biotechnological applications.