PDBsum entry 1uti

Signaling protein regulator

PDB id: 1uti

Contents

Protein chains

57 a.a. *

16 a.a. *

Waters ×63

* Residue conservation analysis

PDB id:

1uti

Name:

Signaling protein regulator

Title:

Mona/gads sh3c in complex with hpk derived peptide

Structure:

Grb2-related adaptor protein 2. Chain: a. Fragment: sh3c domain, residues 265-322. Synonym: gads protein, growth factor receptor binding protein, grb-2- like protein, grb2l, hematopoietic cell-associated adaptor protein grpl, grb-2-related monocytic adapter protein, monocytic adapter, mona, adapter protein grid. Engineered: yes. Mitogen-activated protein kinase kinase kinase kinase 1.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 10090

Biol. unit:

Dimer (from PDB file)

Resolution:

1.50Å R-factor: 0.208 R-free: 0.221

Authors:

M.Lewitzky,M.Harkiolaki,M.C.Domart,S.M.Feller

Key ref:

M.Lewitzky et al. (2004). Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix. J Biol Chem, 279, 28724-28732. PubMed id: 15100220 DOI: 10.1074/jbc.M402745200

Date:

09-Dec-03 Release date: 06-May-04

Protein chain

O89100  (GRAP2_MOUSE) -  GRB2-related adaptor protein 2 from Mus musculus

Seq: 322 a.a.

Struc: 57 a.a.

Protein chain

P70218  (M4K1_MOUSE) -  Mitogen-activated protein kinase kinase kinase kinase 1 from Mus musculus

Seq: 827 a.a.

Struc: 16 a.a.

Enzyme reactions

• Enzyme class 1: Chain A: E.C.?
• Enzyme class 2: Chain D: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M402745200

J Biol Chem 279:28724-28732 (2004)

PubMed id: 15100220

Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix.

M.Lewitzky, M.Harkiolaki, M.C.Domart, E.Y.Jones, S.M.Feller.

ABSTRACT

Hematopoietic progenitor kinase 1 (HPK1) is implicated in signaling downstream of the T cell receptor. Its non-catalytic, C-terminal half contains several prolinerich motifs, which have been shown to interact with different SH3 domain-containing adaptor proteins in vitro. One of these, Mona/Gads, was also shown to bind HPK1 in mouse T cells in vivo. The region of HPK1 that binds to the Mona/Gads C-terminal SH3 domain has been mapped and shows only very limited similarity to a recently identified high affinity binding motif in SLP-76, another T-cell adaptor. Using isothermal titration calorimetry and x-ray crystallography, the binding of the HPK1 motif to Mona/Gads SH3C has now been characterized in molecular detail. The results indicate that although charge interactions through an RXXK motif are essential for complex formation, a PXXP motif in HPK1 strongly complements binding. This unexpected binding mode therefore differs considerably from the previously described interaction of Mona/Gads SH3C with SLP-76. The crystal structure of the complex highlights the great versatility of SH3 domains, which allows interactions with very different proteins. This currently limits our ability to categorize SH3 binding properties by simple rules.

Selected figure(s)

Figure 2.
FIG. 2. Schematic representation of the Mona/Gads SH3C domain with the bound HPK1 peptide (P5). The depicted view looks down the -barrel arrangement of the SH3 domain. The PPII helix of P5 is highlighted in green, and the 3[10] helix is highlighted in orange.

Figure 5.
FIG. 5. Comparison of the Mona/Gads SH3-HPK1 peptide complex with other such structures. A, stereo view superposition of peptides from three different SH3-peptide complexes. SH3 domains are omitted for clarity. The HPK1 is colored (complex with Mona/Gads SH3C) in green, the Sos peptide (bound to Grb2 SH3N; 1GBQ [PDB] .pdb) is colored in orange, and the UBPY (USP8) peptide (in complex with Stam2 SH3; 1UJ0.pdb) is colored in yellow. Peptide orientation is identical in all three cases with N termini pointing up. B, detail of the interactions between the RXXK motif within the HPK1 peptide and Mona/Gads SH3C. C, the corresponding region from the Sos peptide-Grb2 SH3N complex (1GBQ [PDB] .pdb). For clarity, peptide residues are outlined by a light gray underlay.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 28724-28732) copyright 2004.

Figures were selected by an automated process.