3N85

Crystallographic trimer of HER2 extracellular regions in complex with tryptophan-rich antibody fragment

Summary for 3N85

• Entry DOI: 10.2210/pdb3n85/pdb
• Related: 1IVO 1MOX 1N8Z 1S78 1ZA3 3I2T
• Descriptor: Receptor tyrosine-protein kinase erbB-2, Fab37 Light Chain, Fab37 Heavy Chain, ... (7 entities in total)
• Functional Keywords: her2, erbb2, trp/ser library, phage display, transferase-immune system complex, transferase/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 119434.93

Authors

Eigenbrot, C. (deposition date: 2010-05-27, release date: 2010-07-28, Last modification date: 2024-11-06)

Primary citation

Fisher, R.D.,Ultsch, M.,Lingel, A.,Schaefer, G.,Shao, L.,Birtalan, S.,Sidhu, S.S.,Eigenbrot, C.
Structure of the complex between HER2 and an antibody paratope formed by side chains from tryptophan and serine.
J.Mol.Biol., 402:217-229, 2010

PubMed Abstract: Engineered antibody paratopes with limited sequence diversity permit assessment of the roles played by different amino acid side chains in creating the high-affinity, high-specificity interactions characteristic of antibodies. We describe a paratope raised against the human ErbB family member HER2, using a binary diversity tryptophan/serine library displayed on phage. Fab37 binds to the extracellular domain of HER2 with sub-nanomolar affinity. An X-ray structure at 3.2 A resolution reveals a contact paratope composed almost entirely of tryptophan and serine residues. Mutagenesis experiments reveal which of these side chains are more important for direct antigen interactions and which are more important for conformational flexibility. The crystal lattice contains an unprecedented trimeric arrangement of HER2 closely related to previously observed homodimers of the related epidermal growth factor receptor.

PubMed: 20654626
DOI: 10.1016/j.jmb.2010.07.027

Experimental method

X-RAY DIFFRACTION (3.2 Å)