3VRR

Crystal structure of the tyrosine kinase binding domain of Cbl-c (PL mutant) in complex with phospho-EGFR peptide

Summary for 3VRR

• Entry DOI: 10.2210/pdb3vrr/pdb
• Related: 3VRN 3VRO 3VRP 3VRQ
• Descriptor: Signal transduction protein CBL-C, Epidermal growth factor receptor, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: ptb domain, tkb (tyrosine kinase binding) domain, four-helix bundle (4h), calcium-binding ef hand, divergent sh2 domain, regulator of egfr mediated signal transduction, ubiquitously expressed, protein binding-transferase complex, protein binding/transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (Potential): Q9ULV8; Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• Total number of polymer chains: 2
• Total formula weight: 38372.75

Authors

Takeshita, K.,Tezuka, T.,Isozaki, Y.,Yamashita, E.,Suzuki, M.,Yamanashi, Y.,Yamamoto, T.,Nakagawa, A. (deposition date: 2012-04-13, release date: 2013-03-06, Last modification date: 2024-10-30)

Primary citation

Takeshita, K.,Tezuka, T.,Isozaki, Y.,Yamashita, E.,Suzuki, M.,Kim, M.,Yamanashi, Y.,Yamamoto, T.,Nakagawa, A.
Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c.
J.Biochem., 152:487-495, 2012

PubMed 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.

PubMed: 22888118
DOI: 10.1093/jb/mvs085

Experimental method

X-RAY DIFFRACTION (2 Å)