SOLUTION STRUCTURE OF THE NUMB PTB DOMAIN COMPLEXED TO A NAK PEPTIDE

File:1ddm.gif


PDB ID 1ddm

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Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Related: 2NMB


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



OverviewOverview

The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in vitro. To investigate the structural basis for the promiscuous nature of this protein module, we have determined its solution structure by NMR in a complex with a peptide containing an NMSF sequence derived from the Numb-associated kinase (Nak). The Nak peptide was found to adopt a significantly different structure from that of a GPpY sequence-containing peptide previously determined. In contrast to the helical turn adopted by the GPpY peptide, the Nak peptide forms a beta-turn at the NMSF site followed by another turn near the C-terminus. The Numb PTB domain appears to recognize peptides that differ in both primary and secondary structures by engaging various amounts of the binding surface of the protein. Our results suggest a mechanism through which a single PTB domain might interact with multiple distinct target proteins to control a complex biological process such as asymmetric cell division.

About this StructureAbout this Structure

1DDM is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.

ReferenceReference

Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb., Zwahlen C, Li SC, Kay LE, Pawson T, Forman-Kay JD, EMBO J. 2000 Apr 3;19(7):1505-15. PMID:10747019

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