Figure 1
From: DDR1 autophosphorylation is a result of aggregation into dense clusters
Schematic diagram of wild-type and signalling-defective DDR1 mutants. The extracellular region consists of two globular domains, the N-terminal discoidin (DS) domain and the discoidin-like (DS-like) domain, followed by a highly flexible juxtamembrane (JM) region. The transmembrane (TM) region contains a dimerisation motif. The intracellular catalytic kinase domain is preceded by a large unstructured JM region. The collagen-binding trench in the DS domain is shown in red. Collagen binding to this site in wild-type DDR1 induces phosphorylation of cytoplasmic tyrosine residues in both the JM region and kinase domain (shown as yellow circles). None of the mutants are phosphorylated upon collagen incubation. DDR1-W53A has a mutation in the ligand binding pocket in the DS domain. DDR1-R32E and DDR1-L152E are signalling defective mutants with mutations in the ‘signal patch’ region in the base of the DS domain, near the DS-like domain. DDR1-TM1 is a mutant with impaired transmembrane helix association, and DDR1-K655A is a mutant with impaired catalytic function. The locations of mutations are indicated by red stars, and anti-DDR1 epitopes located in the DS-like domain are symbolised by blue and green ovals for wild-type DDR1.
