2BZ8

N-terminal Sh3 domain of CIN85 bound to Cbl-b peptide

Summary for 2BZ8

• Entry DOI: 10.2210/pdb2bz8/pdb
• Descriptor: SH3-DOMAIN KINASE BINDING PROTEIN 1, SIGNAL TRANSDUCTION PROTEIN CBL-B SH3-BINDING PROTEIN CBL-B, RING FINGER PROTEIN 56, CBL-B, SODIUM ION, ... (4 entities in total)
• Functional Keywords: sh3 domain, cin85 adaptor protein, cbl ubiquitin ligase, endocytosis
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm : Q96B97 Q13191
• Total number of polymer chains: 3
• Total formula weight: 14923.65

Authors

Cardenes, N.,Moncalian, G.,Bravo, J. (deposition date: 2005-08-12, release date: 2005-10-05, Last modification date: 2024-05-08)

Primary citation

Jozic, D.,Cardenes, N.,Lissanu-Deribe, Y.,Moncalian, G.,Hoeller, D.,Groemping, Y.,Dikic, I.,Rittinger, K.,Bravo, J.
Cbl Promotes Clustering of Endocytic Adaptor Proteins
Nat.Struct.Mol.Biol., 12:972-, 2005

PubMed Abstract: The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation.

PubMed: 16228008
DOI: 10.1038/NSMB1000

Experimental method

X-RAY DIFFRACTION (2 Å)