PDBsum entry 2jw4

Signaling protein

PDB id: 2jw4

Contents

Protein chain

72 a.a. *

* Residue conservation analysis

PDB id:

2jw4

Name:

Signaling protein

Title:

Nmr solution structure of the n-terminal sh3 domain of human nckalpha

Structure:

Cytoplasmic protein nck1. Chain: a. Fragment: sh3 1 domain, sequence database residues 1-63. Synonym: nck adaptor protein 1, sh2/sh3 adaptor protein nck-alpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nck1, nck. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

C.M.Santiveri,A.Borroto,L.Simon,M.Rico,A.R.Ortiz,B.Alarcon,M.Jimenez

Key ref:

C.M.Santiveri et al. (2009). Interaction between the N-terminal SH3 domain of Nck-alpha and CD3-epsilon-derived peptides: non-canonical and canonical recognition motifs. Biochim Biophys Acta, 1794, 110-117. PubMed id: 18955169

Date:

05-Oct-07 Release date: 26-Aug-08

Protein chain

P16333  (NCK1_HUMAN) -  SH2/SH3 adapter protein NCK1 from Homo sapiens

Seq: 377 a.a.

Struc: 72 a.a.*

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

Biochim Biophys Acta 1794:110-117 (2009)

PubMed id: 18955169

Interaction between the N-terminal SH3 domain of Nck-alpha and CD3-epsilon-derived peptides: non-canonical and canonical recognition motifs.

C.M.Santiveri, A.Borroto, L.Simón, M.Rico, B.Alarcón, M.A.Jiménez.

ABSTRACT

The first SH3 domain (SH3.1) of Nckalpha specifically recognizes the proline-rich region of CD3varepsilon, a subunit of the T cell receptor complex. We have solved the NMR structure of Nckalpha SH3.1 that shows the characteristic SH3 fold consisting of two antiparallel beta-sheets tightly packed against each other. According to chemical shift mapping analysis, a peptide encompassing residues 150-166 of CD3varepsilon binds at the canonical SH3 binding site. An exhaustive comparison with the structures of other SH3 domains able and unable to bind CD3varepsilon reveals that Nckalpha SH3.1 recognises a non-canonical PxxPxxDY motif that orientates at the binding site as a class II ligand. A positively charged residue (K/R) at position -2 relative to the WW sequence at the beginning of strand beta3 is crucial for PxxDY recognition. A 14-mer optimised Nckalpha SH3.1 ligand was found using a multi-substitution approach. Based on NMR data, this improved ligand binds Nckalpha SH3.1 through a PxxPxRDY motif that combines specific stabilising interactions corresponding to both canonical class II, PxxPx(K/R), and non-canonical PxxPxxDY motifs. This explains its higher capacity for Nckalpha SH3.1 binding relative to the wild type sequence.