5YQG

The structure of 14-3-3 and pNumb peptide

Summary for 5YQG

• Entry DOI: 10.2210/pdb5yqg/pdb
• Descriptor: 14-3-3 protein eta, Peptide from Protein numb homolog (3 entities in total)
• Functional Keywords: complex, phosphorylation, non-canonical, peptide binding protein
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cytoplasm: P68510; Membrane; Peripheral membrane protein: Q9QZS3
• Total number of polymer chains: 6
• Total formula weight: 122767.64

Authors

Chen, X.,Liu, Z.,Wen, W. (deposition date: 2017-11-06, release date: 2018-02-07, Last modification date: 2024-10-23)

Primary citation

Chen, X.,Liu, Z.,Shan, Z.,Yao, W.,Gu, A.,Wen, W.
Structural determinants controlling 14-3-3 recruitment to the endocytic adaptor Numb and dissociation of the Numb/alpha-adaptin complex.
J. Biol. Chem., 293:4149-4158, 2018

PubMed Abstract: Traffic of cargo across membranes helps establish, maintain, and reorganize distinct cellular compartments and is fundamental to many metabolic processes. The cargo-selective endocytic adaptor Numb participates in clathrin-dependent endocytosis by attaching cargoes to the clathrin adaptor α-adaptin. The phosphorylation of Numb at Ser and Ser recruits the regulatory protein 14-3-3, accompanied by the dissociation of Numb from α-adaptin and Numb's translocation from the cortical membrane to the cytosol. However, the molecular mechanisms underlying the Numb-α-adaptin interaction and its regulation by Numb phosphorylation and 14-3-3 recruitment remain poorly understood. Here, biochemical and structural analyses of the Numb·14-3-3 complex revealed that Numb phosphorylation at both Ser and Ser is required for Numb's efficient interaction with 14-3-3. We also discovered that an RQFRF motif surrounding Ser in Numb functions together with the canonical C-terminal DPF motif, required for Numb's interaction with α-adaptin, to form a stable complex with α-adaptin. Of note, we provide evidence that the phosphorylation-induced binding of 14-3-3 to Numb directly competes with the binding of α-adaptin to Numb. Our findings suggest a potential mechanism governing the dynamic assembly of Numb with α-adaptin or 14-3-3. This dual-site recognition of Numb by α-adaptin may have implications for other α-adaptin targets. We propose that the newly identified α-adaptin-binding site surrounding Ser in Numb functions as a triggering mechanism for the dynamic dissociation of the Numb·α-adaptin complex.

PubMed: 29382713
DOI: 10.1074/jbc.RA117.000897

Experimental method

X-RAY DIFFRACTION (2.1 Å)