General Information

Database Accession: DI1000298

Name: XLP protein SAP SH2 domain in complex with a phosphorylated SLAM peptide

PDB ID: 1d4w PDB

Experimental method: X-ray (1.80 Å)

Source organism: Homo sapiens

Proof of disorder: Inferred from motif

Primary publication of the structure:

Poy F, Yaffe MB, Sayos J, Saxena K, Morra M, Sumegi J, Cantley LC, Terhorst C, Eck MJ
Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition.
(1999) Mol. Cell 4: 555-61

PMID: 10549287 PubMed

Abstract:

SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I).

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

protein binding Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules). GeneOntology

Biological process:

adaptive immune response An immune response based on directed amplification of specific receptors for antigen produced through a somatic diversification process, and allowing for enhanced response to subsequent exposures to the same antigen (immunological memory). GeneOntology

innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. GeneOntology

single-organism cellular process Any process that is carried out at the cellular level, occurring within a single organism. GeneOntology

cell communication Any process that mediates interactions between a cell and its surroundings. Encompasses interactions such as signaling or attachment between one cell and another cell, between a cell and an extracellular matrix, or between a cell and any other aspect of its environment. GeneOntology

positive regulation of signal transduction Any process that activates or increases the frequency, rate or extent of signal transduction. GeneOntology

regulation of lymphocyte mediated immunity Any process that modulates the frequency, rate, or extent of lymphocyte mediated immunity. GeneOntology

regulation of immune response Any process that modulates the frequency, rate or extent of the immune response, the immunological reaction of an organism to an immunogenic stimulus. GeneOntology

Cellular component:

cytoplasm All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: C, A

Notes: Chains B and D were removed as chains A and C represent the biologically relevant interaction.

Chain C

Name: Signaling lymphocytic activation molecule Disordered Inferred from motif

Source organism: Homo sapiens

Length: 11 residues

Sequence:Sequence according to PDB SEQRESKSLTIYAQVQK

The sequence contains the following modified/non-standard residues:

• phosphotyrosine (Y) at position 281 (PDB position: 281)

UniProtKB AC: Q13291 (positions: 276-286) UniProt Coverage: 3.3%

UniRef90 AC: UniRef90_Q13291 (positions: 276-286) UniRef90

Chain A

Name: SH2 domain-containing protein 1A Ordered

Source organism: Homo sapiens

Length: 104 residues

Sequence:Sequence according to PDB SEQRESMDAVAVYHGKISRETGEKLLLATGLDGSYLLRDSESVPGVYCLCVLYHGYIYTYRVSQTETGSWSAETAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEK

UniProtKB AC: O60880 (positions: 1-104) UniProt Coverage: 81.3%

UniRef90 AC: UniRef90_O60880 (positions: 1-104) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain C: Disordered Inferred from motif

The protein region involved in the interaction contains a known functional linear motif (LIG_TYR_ITSM).

Chain A: Ordered

The SH2 domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00017). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 1ab2.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

There is 1 related structure in the Protein Data Bank:

• 1ka6

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