PDBsum entry 1fu5

Peptide binding protein

PDB id

1fu5

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Contents

			Protein chains

					111 a.a. *


					15 a.a. *

* Residue conservation analysis

PDB id:

1fu5

Links
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Name:

Peptide binding protein

Title:

Nmr structure of the n-sh2 domain of the p85 subunit of pi3-kinase complexed to a doubly phosphorylated peptide derived from polyomavirus middle t antigen

Structure:

Phosphatidylinositol 3-kinase regulatory alpha subunit. Chain: a. Fragment: residues 321 to 431 of p85, n-sh2 (src homology 2) domain. Synonym: pi3-kinase p85-alpha subunit, ptdins-3-kinase p85-alpha, pi3k. Engineered: yes. Doubly phosphorylated middle t antigen. Chain: b. Fragment: residues 312 to 326 of mt antigen, y315 and y322

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: mt peptide was synthesized by the tufts protein chemistry facility

NMR struc:

1 models

Authors:

T.Weber,B.Schaffhausen,Y.Liu,U.L.Guenther

Key ref:

T.Weber et al. (2000). NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site. Biochemistry, 39, 15860-15869. PubMed id: 11123912 DOI: 10.1021/bi001474d

Date:

14-Sep-00

Release date:

21-Feb-01

PROCHECK

	Headers

	References

Protein chain

Q63787 (P85A_RAT) - Phosphatidylinositol 3-kinase regulatory subunit alpha from Rattus norvegicus

Seq: Struc:

Seq: Struc:					724 a.a. 111 a.a.*

Protein chain

P03077 (MT_POVMA) - Middle T antigen from Murine polyomavirus (strain A2)

Seq: Struc:					421 a.a. 15 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1021/bi001474d	Biochemistry 39:15860-15869 (2000)
PubMed id: 11123912

NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site.
T.Weber, B.Schaffhausen, Y.Liu, U.L.Günther.

ABSTRACT

The N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K) has a higher affinity for a peptide with two phosphotyrosines than for the same peptide with only one. This unexpected result was not observed for the C-terminal SH2 from the same protein. NMR structural analysis has been used to understand the behavior of the N-SH2. The structure of the free SH2 domain has been compared to that of the SH2 complexed with a doubly phosphorylated peptide derived from polyomavirus middle T antigen (MT). The structure of the free SH2 domain shows some differences from previous NMR and X-ray structures. In the N-SH2 complexed with a doubly phosphorylated peptide, a second site for phosphotyrosine interaction has been identified. Further, line shapes of NMR signals showed that the SH2 protein-ligand complex is subject to temperature-dependent conformational mobility. Conformational mobility is also supported by the spectra of the ligand peptide. A binding model which accounts for these results is developed.

Literature references that cite this PDB file's key reference

PubMed id

Reference

18767163

W.Gan, and B.Roux (2009).
Binding specificity of SH2 domains: insight from free energy simulations.

Proteins, 74, 996.

18260110

I.Lappalainen, J.Thusberg, B.Shen, and M.Vihinen (2008).
Genome wide analysis of pathogenic SH2 domain mutations.

Proteins, 72, 779-792.

17894853

C.J.Porter, J.M.Matthews, J.P.Mackay, S.E.Pursglove, J.W.Schmidberger, P.J.Leedman, S.C.Pero, D.N.Krag, M.C.Wilce, and J.A.Wilce (2007).
Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation.

BMC Struct Biol, 7, 58.

PDB code:

2qms

15520002

A.Suenaga, N.Takada, M.Hatakeyama, M.Ichikawa, X.Yu, K.Tomii, N.Okimoto, N.Futatsugi, T.Narumi, M.Shirouzu, S.Yokoyama, A.Konagaya, and M.Taiji (2005).
Novel mechanism of interaction of p85 subunit of phosphatidylinositol 3-kinase and ErbB3 receptor-derived phosphotyrosyl peptides.

J Biol Chem, 280, 1321-1326.

15657912

G.S.Akerman, B.A.Rosenzweig, O.E.Domon, C.A.Tsai, M.E.Bishop, L.J.McGarrity, J.T.Macgregor, F.D.Sistare, J.J.Chen, and S.M.Morris (2005).
Alterations in gene expression profiles and the DNA-damage response in ionizing radiation-exposed TK6 cells.

Environ Mol Mutagen, 45, 188-205.

15932879

S.C.Shekar, H.Wu, Z.Fu, S.C.Yip, Nagajyothi, S.M.Cahill, M.E.Girvin, and J.M.Backer (2005).
Mechanism of constitutive phosphoinositide 3-kinase activation by oncogenic mutants of the p85 regulatory subunit.

J Biol Chem, 280, 27850-27855.

15096211

Z.Su, P.Xu, and F.Ni (2004).
Single phosphorylation of Tyr304 in the cytoplasmic tail of ephrin B2 confers high-affinity and bifunctional binding to both the SH2 domain of Grb4 and the PDZ domain of the PDZ-RGS3 protein.

Eur J Biochem, 271, 1725-1736.

12151228

S.Djordjevic, and P.C.Driscoll (2002).
Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases.

Trends Biochem Sci, 27, 426-432.

11746693

G.M.Verkhivker, D.Bouzida, D.K.Gehlhaar, P.A.Rejto, L.Schaffer, S.Arthurs, A.B.Colson, S.T.Freer, V.Larson, B.A.Luty, T.Marrone, and P.W.Rose (2001).
Hierarchy of simulation models in predicting molecular recognition mechanisms from the binding energy landscapes: structural analysis of the peptide complexes with SH2 domains.

Proteins, 45, 456-470.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.