2K7A

Ensemble Structures of the binary complex between the SH3 and SH2 domain of interleukin-2 tyrosine kinase.

Summary for 2K7A

• Entry DOI: 10.2210/pdb2k7a/pdb
• Related: 1awj 1luk 1lun 2K79 2etz 2rna
• NMR Information: BMRB: 16809
• Descriptor: SH3 domain of Tyrosine-protein kinase ITK/TSK, SH2 domain of Tyrosine-protein kinase ITK/TSK (2 entities in total)
• Functional Keywords: sh3, sh2, novel, cis, atp-binding, cell membrane, kinase, membrane, metal-binding, nucleotide-binding, phosphoprotein, sh2 domain, sh3 domain, transferase, tyrosine-protein kinase, zinc, zinc-finger
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 20034.27

Authors

Andreotti, A.H.,Severin, A.J.,Fulton, D.B. (deposition date: 2008-08-08, release date: 2009-03-10, Last modification date: 2024-05-01)

Primary citation

Severin, A.,Joseph, R.E.,Boyken, S.,Fulton, D.B.,Andreotti, A.H.
Proline isomerization preorganizes the Itk SH2 domain for binding to the Itk SH3 domain.
J.Mol.Biol., 387:726-743, 2009

PubMed Abstract: We report here the NMR-derived structure of the binary complex formed by the interleukin-2 tyrosine kinase (Itk) Src homology 3 (SH3) and Src homology 2 (SH2) domains. The interaction is independent of both a phosphotyrosine motif and a proline-rich sequence, the classical targets of the SH2 and SH3 domains, respectively. The Itk SH3/SH2 structure reveals the molecular details of this nonclassical interaction and provides a clear picture for how the previously described prolyl cis/trans isomerization present in the Itk SH2 domain mediates SH3 binding. The higher-affinity cis SH2 conformer is preorganized to form a hydrophobic interface with the SH3 domain. The structure also provides insight into how autophosphorylation in the Itk SH3 domain might increase the affinity of the intermolecular SH3/SH2 interaction. Finally, we can compare this Itk complex with other examples of SH3 and SH2 domains engaging their ligands in a nonclassical manner. These small binding domains exhibit a surprising level of diversity in their binding repertoires.

PubMed: 19361414
DOI: 10.1016/j.jmb.2009.02.012

Experimental method

SOLUTION NMR