PDBsum entry 2n2a

Membrane protein

PDB id: 2n2a

Contents

Protein chains

58 a.a.

PDB id:

2n2a

Name:

Membrane protein

Title:

Spatial structure of her2/erbb2 dimeric transmembrane domain in the presence of cytoplasmic juxtamembrane domains

Structure:

Receptor tyrosine-protein kinase erbb-2. Chain: a, b. Fragment: transmembrane domain (unp residues 644-700). Synonym: metastatic lymph node gene 19 protein, mln 19, proto- oncogene neu, proto-oncogenE C-erbb-2, tyrosine kinase-type cell surface receptor her2, p185erbb2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: erbb2, her2, mln19, neu, ngl. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

10 models

Authors:

P.E.Bragin,K.S.Mineev,E.Bocharov,O.Bocharova,A.Arseniev

Key ref:

P.E.Bragin et al. (2016). HER2 Transmembrane Domain Dimerization Coupled with Self-Association of Membrane-Embedded Cytoplasmic Juxtamembrane Regions. J Mol Biol, 428, 52-61. PubMed id: 26585403 DOI: 10.1016/j.jmb.2015.11.007

Date:

05-May-15 Release date: 24-Feb-16

Protein chains

P04626  (ERBB2_HUMAN) -  Receptor tyrosine-protein kinase erbB-2 from Homo sapiens

Seq: 1255 a.a.

Struc: 58 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.jmb.2015.11.007

J Mol Biol 428:52-61 (2016)

PubMed id: 26585403

HER2 Transmembrane Domain Dimerization Coupled with Self-Association of Membrane-Embedded Cytoplasmic Juxtamembrane Regions.

P.E.Bragin, K.S.Mineev, O.V.Bocharova, P.E.Volynsky, E.V.Bocharov, A.S.Arseniev.

ABSTRACT

Receptor tyrosine kinases of the human epidermal growth factor receptor (HER or ErbB) family transduce biochemical signals across plasma membrane, playing a significant role in vital cellular processes and in various cancers. Inactive HER/ErbB receptors exist in equilibrium between the monomeric and unspecified pre-dimerized states. After ligand binding, the receptors are involved in strong lateral dimerization with proper assembly of their extracellular ligand-binding, single-span transmembrane, and cytoplasmic kinase domains. The dimeric conformation of the HER2 transmembrane domain that is believed to support the cytoplasmic kinase domain configuration corresponding to the receptor active state was previously described in lipid bicelles. Here we used high-resolution NMR spectroscopy in another membrane-mimicking micellar environment and identified an alternative HER2 transmembrane domain dimerization coupled with self-association of membrane-embedded cytoplasmic juxtamembrane region. Such a dimerization mode appears to be capable of effectively inhibiting the receptor kinase activity. This finding refines the molecular mechanism regarding the signal propagation steps from the extracellular to cytoplasmic domains of HER/ErbB receptors.