The insulin and EGF receptor structures: new insights into ligand-induced receptor activation.
The insulin receptor (IR) and epidermal growth factor receptor (EGFR; also known as ErbB) families exhibit similarities in the composition of their ectodomains. The past five years have seen structures determined for all members of the EGFR family including some complexes with ligand or monoclonal antibody fragments. These structures have led to a clearer understanding of their mechanism of activation and inhibition. By contrast, obtaining equivalent understanding of the IR family has lagged behind. However, within the past year, structures of partial and complete ectodomains of the IR have been published that show that the extracellular region of the receptor adopts an unexpected 'inverted V' conformation relative to the cell membrane. This is very different from the folded-over (tethered) conformation of the unactivated EGFR and provides insight into the potential mechanism of activation of the IR.
Ward
Colin W
CW
Australian Commonwealth Scientific and Research Organization Molecular and Health Technologies, 343 Royal Parade, Parkville, Victoria 3052, Australia. Colin.Ward@csiro.au
Lawrence
Michael C
MC
Streltsov
Victor A
VA
Adams
Timothy E
TE
McKern
Neil M
NM
D000818:Animals; D000937:Antigen-Antibody Reactions; D019281:Dimerization; D066246:ErbB Receptors / Q000737:chemistry* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000502:physiology; D011972:Receptor, Insulin / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D007328:Insulin; D008024:Ligands; D066246:ErbB Receptors; D011972:Receptor, Insulin