PDBsum entry 4zxb

Hormone receptor/immune system

PDB id: 4zxb

Contents

Protein chains

214 a.a.

218 a.a.

187 a.a.

182 a.a.

800 a.a.

Ligands

NAG-NAG-FUC ×3

NAG-NAG-BMA

NAG-NAG-BMA-MAN-NAG-FUC

NAG-FUC ×2

NAG ×3

PDB id:

4zxb

Name:

Hormone receptor/immune system

Title:

Structure of the human insulin receptor ectodomain, irdeltabeta construct, in complex with four fab molecules

Structure:

Fab 83-7 heavy chain. Chain: a. Engineered: yes. Fab 83-7 light chain. Chain: b. Engineered: yes. Fab 83-14 heavy chain. Chain: c. Engineered: yes.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: mus musculus. Expression_system_taxid: 10090. Gene: igh-1a. Gene: igkc, igk-c. Homo sapiens. Organism_taxid: 9606.

Resolution:

3.30Å R-factor: 0.207 R-free: 0.237

Authors:

T.Croll,B.J.Smith,M.B.Margetts,J.Whittaker,M.A.Weiss,C.W.Ward, M.C.Lawrence

Key ref:

T.I.Croll et al. (2016). Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. Structure, 24, 469-476. PubMed id: 26853939 DOI: 10.1016/j.str.2015.12.014

Date:

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

Supersedes:

3loh

Protein chain

U5LP42  (U5LP42_MOUSE) -  Anti-H5N1 hemagglutinin monoclonal anitbody H5M9 heavy chain (Fragment) from Mus musculus

Seq: 463 a.a.

Struc: 214 a.a.*

Protein chain

P01837  (IGKC_MOUSE) -  Immunoglobulin kappa constant from Mus musculus

Seq: 107 a.a.

Struc: 218 a.a.

Protein chain

P01865  (GCAM_MOUSE) -  Immunoglobulin heavy constant gamma 2A from Mus musculus

Seq: 398 a.a.

Struc: 187 a.a.

Protein chain

A2P1G9  (A2P1G9_MOUSE) -  Kappa light chain (Fragment) from Mus musculus

Seq: 219 a.a.

Struc: 182 a.a.*

Protein chain

P06213  (INSR_HUMAN) -  Insulin receptor from Homo sapiens

Seq: 1382 a.a.

Struc: 800 a.a.*

* PDB and UniProt seqs differ at 113 residue positions (black crosses)

Enzyme reactions

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

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] (Bound ligand (Het Group name = NAG) matches with 41.38% similarity) + ADP + H(+)

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

Added reference

DOI no: 10.1016/j.str.2015.12.014

Structure 24:469-476 (2016)

PubMed id: 26853939

Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain.

T.I.Croll, B.J.Smith, M.B.Margetts, J.Whittaker, M.A.Weiss, C.W.Ward, M.C.Lawrence.

ABSTRACT

Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.