PDBsum entry: 2nmb

Cell cycle/gene regulation

PDB id: 2nmb

Contents

Protein chain

147 a.a. *

Ligands

ALA-TYR-ILE-GLY-PRO-PTR-LEU

* Residue conservation analysis

PDB id:

2nmb

Name:

Cell cycle/gene regulation

Title:

Dnumb ptb domain complexed with a phosphotyrosine peptide, nmr, ensemble of structures.

Structure:

Protein (numb protein). Chain: a. Fragment: ptb domain. Engineered: yes. Protein (gppy peptide). Chain: b. Engineered: yes. Other_details: chemically synthesized

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: numb. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes

NMR struc:

14 models

Authors:

S.-C.Li,C.Zwahlen,S.J.F.Vincent,C.J.Mcglade,T.Pawson, J.D.Forman-Kay

Key ref:

S.C.Li et al. (1998). Structure of a Numb PTB domain-peptide complex suggests a basis for diverse binding specificity. Nat Struct Biol, 5, 1075-1083. PubMed id: 9846878 DOI: 10.1038/4185

Date:

29-Oct-98 Release date: 04-Nov-98

Protein chain

P16554  (NUMB_DROME) -  Protein numb

Seq: 556 a.a.

Struc: 147 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1038/4185

Nat Struct Biol 5:1075-1083 (1998)

PubMed id: 9846878

Structure of a Numb PTB domain-peptide complex suggests a basis for diverse binding specificity.

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

ABSTRACT

The phosphotyrosine-binding (PTB) domain of Numb, a protein involved in asymmetric cell division, has recently been shown to bind to the adapter protein Lnx through an LDNPAY sequence, to the Numb-associated kinase (Nak) through a sequence that does not contain an NPXY motif and to GP(p)Y-containing peptides obtained from library screening. We show here that these diverse peptide sequences bind with comparable affinities to the Numb PTB domain at a common binding site on the surface of the protein. The NMR structure of the Numb PTB domain in complex with a GPpY-containing peptide reveals a novel mechanism of binding with the peptide in a helical turn that does not hydrogen bond to the PTB domain beta-sheet. These results suggest that PTB domains can potentially have multiple modes of peptide recognition and provide a structural basis from which the multiple functions of the Numb PTB domain during asymmetric cell division could arise.

Selected figure(s)

Figure 2.
Figure 2. Solution structure of the dNumb PTB domain−GPpY peptide complex. a, Superposition of the 14 final structures. b, Schematic ribbon diagram of the backbone showing helices in green, -strands in yellow and the peptide in red. c, Interactions of the peptide with the PTB domain. Figure generated using MOLMOL^47.

Figure 3.
Figure 3. Structure-based alignment^34 of sequences of the dNumb, X11^14, Shc^8 and IRS-1^10 PTB domains, with residues of the dNumb PTB domain highlighted in green for helices and yellow for -strands. Residues in the PTB domains that have direct contacts to their target peptides are highlighted in red.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1998, 5, 1075-1083) copyright 1998.

Figures were selected by an automated process.