PDBsum entry 4m4z

Signaling protein

PDB id: 4m4z

Contents

Protein chain

152 a.a.

Waters ×64

PDB id:

4m4z

Name:

Signaling protein

Title:

Sh3 and sh2 domains of human src-like adaptor protein 2 (slap2)

Structure:

Src-like-adapter 2. Chain: a. Fragment: unp residues 29-193. Synonym: modulator of antigen receptor signaling, mars, src-like adapter protein 2, slap-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: c20orf156, sla2, slap2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.184 R-free: 0.225

Authors:

L.E.Wybenga-Groot,C.J.Mcglade

Key ref:

L.E.Wybenga-Groot and C.J.McGlade (2013). Crystal structure of Src-like adaptor protein 2 reveals close association of SH3 and SH2 domains through β-sheet formation. Cell Signal, 25, 2702-2708. PubMed id: 24018043 DOI: 10.1016/j.cellsig.2013.08.040

Date:

07-Aug-13 Release date: 06-Nov-13

Protein chain

Q9H6Q3  (SLAP2_HUMAN) -  Src-like-adapter 2 from Homo sapiens

Seq: 261 a.a.

Struc: 152 a.a.

DOI no: 10.1016/j.cellsig.2013.08.040

Cell Signal 25:2702-2708 (2013)

PubMed id: 24018043

Crystal structure of Src-like adaptor protein 2 reveals close association of SH3 and SH2 domains through β-sheet formation.

L.E.Wybenga-Groot, C.J.McGlade.

ABSTRACT

The Src-like adaptor proteins (SLAP/SLAP2) are key components of Cbl-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling in hematopoietic cells. SLAP and SLAP2 consist of adjacent SH3 and SH2 domains that are most similar in sequence to Src family kinases (SFKs). Notably, the SH3-SH2 connector sequence is significantly shorter in SLAP/SLAP2 than in SFKs. To understand the structural implication of a short SH3-SH2 connector sequence, we solved the crystal structure of a protein encompassing the SH3 domain, SH3-SH2 connector, and SH2 domain of SLAP2 (SLAP2-32). While both domains adopt typical folds, the short SH3-SH2 connector places them in close association. Strand βe of the SH3 domain interacts with strand βA of the SH2 domain, resulting in the formation of a continuous β sheet that spans the length of the protein. Disruption of the SH3/SH2 interface through mutagenesis decreases SLAP-32 stability in vitro, consistent with inter-domain binding being an important component of SLAP2 structure and function. The canonical peptide binding pockets of the SH3 and SH2 domains are fully accessible, in contrast to other protein structures that display direct interaction between SH3 and SH2 domains, in which either peptide binding surface is obstructed by the interaction. Our results reveal potential sites of novel interaction for SH3 and SH2 domains, and illustrate the adaptability of SH2 and SH3 domains in mediating interactions. As well, our results suggest that the SH3 and SH2 domains of SLAP2 function interdependently, with implications on their mode of substrate binding.