Fig. 7: TCPTP autoinhibition and activation is driven by intrinsically disordered protein: protein interactions. | Nature Communications

Fig. 7: TCPTP autoinhibition and activation is driven by intrinsically disordered protein: protein interactions.

From: The catalytic activity of TCPTP is auto-regulated by its intrinsically disordered tail and activated by Integrin alpha-1

Fig. 7

a Inactive state of TCPTP - Intramolecular interaction of the IDR TCPTP C-terminal tail with TCPTPCAT via the N-surface (navy) leads to the formation of TCPTP’s autoinhibitory conformation. b Active form of TCPTP – the IDR C-terminal cytoplasmic tail of ITGA1 binds TCPTPCAT via loops L1, L2 and displaces the intramolecular interaction with the IDR TCPTP C-terminal tail, which relieves the autoinhibitory conformation, leading to efficient dephosphorylation of EGFR. Recruitment and activation of TCPTP by ITGA1 requires collagen binding to integrin α1β130, as a result, conformational changes occur in the integrin α1β1 heterodimer, which allow the ITGA1 cytoplasmic tail to become exposed from β153, leading to recruitment and activation of TCPTP.

Back to article page