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Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c.

Takeshita K, Tezuka T, Isozaki Y, Yamashita E, Suzuki M, Kim M, Yamanashi Y, Yamamoto T, Nakagawa A
J Biochem 152 487-95 (2012)
Related entries: 3vrn, 3vro, 3vrp, 3vrq

Cited: 3 times
EuropePMC logo PMID: 22888118

Abstract

Through their ubiquitin ligase activity, Cbl-family proteins suppress signalling mediated by protein-tyrosine kinases (PTKs), but can also function as adaptor proteins to positively regulate signalling. The tyrosine kinase binding (TKB) domain of this family is critical for binding with tyrosine-phosphorylated target proteins. Here, we analysed the crystal structure of the TKB domain of Cbl-c/Cbl-3 (Cbl-c TKB), which is a distinct member of the mammalian Cbl-family. In comparison with Cbl TKB, Cbl-c TKB showed restricted structural flexibility upon phosphopeptide binding. A mutation in Cbl-c TKB augmenting this flexibility enhanced its binding to target phosphoproteins. These results suggest that proteins, post-translational modifications or mutations that alter structural flexibility of the TKB domain of Cbl-family proteins could regulate their binding to target phosphoproteins and thereby, affect PTK-mediated signalling.

Articles citing this publication (3)

  1. High-yield cell-free synthesis of human EGFR by IRES-mediated protein translation in a continuous exchange cell-free reaction format. Quast RB, Sonnabend A, Stech M, Wüstenhagen DA, Kubick S. Sci Rep 6 30399 (2016)
  2. Decreased pulmonary c-Cbl expression and tyrosine phosphorylation in the nitrofen-induced rat model of congenital diaphragmatic hernia. Friedmacher F, Gosemann JH, Takahashi H, Corcionivoschi N, Puri P. Pediatr. Surg. Int. 29 19-24 (2013)
  3. Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis. Zhao XC, Wang GZ, Wen ZS, Zhou YC, Hu Q, Zhang B, Qu LW, Gao SH, Liu J, Ma L, Zhang YF, Zhang C, Yu H, Zhang DL, Wang M, Wang CL, Huang YC, Liu ZH, Zhao Y, Chen L, Zhou GB. EBioMedicine 53 102689 (2020)


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