ISDA: 5O4O

Deposition Date 2017-05-30

Release Date 2018-05-16

Last Version Date 2024-10-23

Entry Detail

PDB ID:

5O4O

Keywords:

IMMUNE SYSTEM

Title:

HER3 in complex with Fab MF3178

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Homo sapiens

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

3.40 Å

R-Value Free:

0.26

R-Value Work:

0.21

R-Value Observed:

0.21

Space Group:

I 1 2 1

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Macromolecular Entities

Polymer Type:polypeptide(L)
Molecule:MF3178 FAB light chain
Chain IDs:A
Chain Length:214
Number of Molecules:1
Biological Source:Homo sapiens

Polymer Type:polypeptide(L)
Molecule:MF3178 FAB heavy chain
Chain IDs:B
Chain Length:250
Number of Molecules:1
Biological Source:Homo sapiens

Structures with similar UniProt ID

Structural Superimposition Protein Blast

Polymer Type:polypeptide(L)
Molecule:Receptor tyrosine-protein kin
Gene (Uniprot):ERBB3
Chain IDs:C
Chain Length:649
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:P21860 Pfam ID:PF01030, PF00757, PF14843 EC:2.7.10.1

Ligand Molecules

NAG

Primary Citation

Unbiased Combinatorial Screening Identifies a Bispecific IgG1 that Potently Inhibits HER3 Signaling via HER2-Guided Ligand Blockade.

Geuijen, C.A.W, De Nardis, C, Maussang, D, Rovers, E, Gallenne, T, Hendriks, L.J.A, Visser, T, Nijhuis, R, Logtenberg, T, de Kruif, J, Gros, P, Throsby, M.Show

Cancer Cell 33 922 936.e10 (2018)

PMID: 29763625 DOI: 10.1016/j.ccell.2018.04.003

Abstact

HER2-driven cancers require phosphatidylinositide-3 kinase (PI3K)/Akt signaling through HER3 to promote tumor growth and survival. The therapeutic benefit of HER2-targeting agents, which depend on PI3K/Akt inhibition, can be overcome by hyperactivation of the heregulin (HRG)/HER3 pathway. Here we describe an unbiased phenotypic combinatorial screening approach to identify a bispecific immunoglobulin G1 (IgG1) antibody against HER2 and HER3. In tumor models resistant to HER2-targeting agents, the bispecific IgG1 potently inhibits the HRG/HER3 pathway and downstream PI3K/Akt signaling via a "dock & block" mechanism. This bispecific IgG1 is a potentially effective therapy for breast cancer and other tumors with hyperactivated HRG/HER3 signaling.

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Protein

Chemical

Disease

Primary Citation of related structures

Abstact

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