 |
PDBsum entry 6pyh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Signaling protein/hormone
|
PDB id
|
|
|
|
6pyh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
793 a.a.
|
|
|
|
|
|
|
|
|
|
|
57 a.a.
|
|
|
|
|
|
|
|
|
|
|
798 a.a.
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Signaling protein/hormone
|
|
|
Title:
|
|
Cryo-em structure of full-length igf1r-igf1 complex. Only the extracellular region of the complex is resolved.
|
|
Structure:
|
|
Insulin-like growth factor 1 receptor. Chain: a, d. Synonym: insulin-like growth factor i receptor,igf-i receptor. Engineered: yes. Insulin-like growth factor i. Chain: b. Synonym: igf-i,mechano growth factor,mgf,somatomedin-c. Engineered: yes
|
|
Source:
|
|
Mus musculus. Mouse. Organism_taxid: 10090. Gene: igf1r. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293. Homo sapiens. Human.
|
|
Authors:
|
|
J.Li,E.Choi,H.T.Yu,X.C.Bai
|
|
Key ref:
|
|
J.Li
et al.
(2019).
Structural basis of the activation of type 1 insulin-like growth factor receptor.
Nat Commun,
10,
4567.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
29-Jul-19
|
Release date:
|
23-Oct-19
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q60751
(IGF1R_MOUSE) -
Insulin-like growth factor 1 receptor from Mus musculus
|
|
|
|
Seq:
Struc:
|
|
|
|
1373 a.a.
793 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
Chains A, D:
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]
|
+
|
ADP
|
+
|
H(+)
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
Nat Commun
10:4567
(2019)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structural basis of the activation of type 1 insulin-like growth factor receptor.
|
|
J.Li,
E.Choi,
H.Yu,
X.C.Bai.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase
that regulates cell growth and proliferation, and can be activated by IGF1,
IGF2, and insulin. Here, we report the cryo-EM structure of full-length
IGF1R-IGF1 complex in the active state. This structure reveals that only one
IGF1 molecule binds the Γ-shaped asymmetric IGF1R dimer. The IGF1-binding site
is formed by the L1 and CR domains of one IGF1R protomer and the α-CT and
FnIII-1 domains of the other. The liganded α-CT forms a rigid beam-like
structure with the unliganded α-CT, which hinders the conformational change of
the unliganded α-CT required for binding of a second IGF1 molecule. We further
identify an L1-FnIII-2 interaction that mediates the dimerization of
membrane-proximal domains of IGF1R. This interaction is required for optimal
receptor activation. Our study identifies a source of the negative cooperativity
in IGF1 binding to IGF1R and reveals the structural basis of IGF1R activation.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
| |
Links
