PDBsum entry: 1ddm

Signaling protein/transferase

PDB id: 1ddm

Contents

Protein chains

135 a.a. *

11 a.a. *

* Residue conservation analysis

PDB id:

1ddm

Name:

Signaling protein/transferase

Title:

Solution structure of the numb ptb domain complexed to a nak peptide

Structure:

Numb protein. Chain: a. Fragment: phosphotyrosine binding domain (ptb). Engineered: yes. Other_details: cell fate determinant protein. Numb associate kinase. Chain: b. Fragment: c-terminal nak 1437-1447. Synonym: nak.

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562. Organism_taxid: 7227

NMR struc:

20 models

Authors:

C.Zwahlen,S.C.Li,L.E.Kay,T.Pawson,J.D.Forman-Kay

Key ref:

C.Zwahlen et al. (2000). Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb. EMBO J, 19, 1505-1515. PubMed id: 10747019 DOI: 10.1093/emboj/19.7.1505

Date:

11-Nov-99 Release date: 10-Apr-00

Protein chain

P16554  (NUMB_DROME) -  Protein numb

Seq: 556 a.a.

Struc: 135 a.a.

Protein chain

No UniProt id for this chain

DOI no: 10.1093/emboj/19.7.1505

EMBO J 19:1505-1515 (2000)

PubMed id: 10747019

Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb.

C.Zwahlen, S.C.Li, L.E.Kay, T.Pawson, J.D.Forman-Kay.

ABSTRACT

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.

Selected figure(s)

Figure 2.
Figure 2 Solution structure of the Numb PTB domain–Nak peptide complex. (A) Stereo representation of a superposition of the 20 final structures. (B) Schematic ribbon diagram of the backbone. The protein is shown in blue and the peptide in orange. The side chains of the Nak peptide are labeled. The figure was generated using MOLMOL (Koradi et al., 1996).

Figure 4.
Figure 4 Ribbon representations of (A) the Numb PTB domain–Nak peptide complex, (B) the Numb PTB domain–GPpY peptide complex, (C) the IRS-1 PTB domain–IL-4R peptide complex (Zhou et al., 1996) and (D) the X11 PTB domain– APP peptide complex (Zhang et al., 1997) shown in the same orientation. Proteins are in blue and peptides in red.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 1505-1515) copyright 2000.

Figures were selected by the author.