1F2F

SRC SH2 THREF1TRP MUTANT

1F2F の概要

• エントリーDOI: 10.2210/pdb1f2f/pdb
• 関連するPDBエントリー: 1F1W
• 分子名称: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE SRC, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: src, sh2 domain, specificity switch, transferase
• 由来する生物種: Gallus gallus (chicken)
• 細胞内の位置: Cell membrane (By similarity): P00523
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12153.62

構造登録者

Kimber, M.S.,Nachman, J.,Cunningham, A.M.,Gish, G.D.,Pawson, T.,Pai, E.F. (登録日: 2000-05-24, 公開日: 2000-07-06, 最終更新日: 2024-02-07)

主引用文献

Kimber, M.S.,Nachman, J.,Cunningham, A.M.,Gish, G.D.,Pawson, T.,Pai, E.F.
Structural basis for specificity switching of the Src SH2 domain.
Mol.Cell, 5:1043-1049, 2000

PubMed Abstract: The Src SH2 domain binds pYEEI-containing phosphopeptides in an extended conformation with a hydrophobic pocket, which includes ThrEF1, binding Ile(pY +3). Mutating ThrEF1 to tryptophan switches specificity to an Asn(pY +2) requirement, yielding a biological mimic of the Grb2 SH2 domain. Here we show that the Src ThrEF1Trp SH2 domain mutant binds pYVNV phosphopeptides in a beta turn conformation, which, despite differing conformations of the interacting tryptophan, closely resembles the native Grb2/pYVNV cognate peptide binding mode. The ThrEF1Trp substitution therefore switches specificity by physically occluding the pTyr +3 binding pocket and by providing additional interaction surface area for Asn(pY +2). This demonstrates structurally how novel SH2 domain specificities may rapidly evolve through single amino acid substitutions and suggests how new signaling pathways may develop.

PubMed: 10911998
DOI: 10.1016/S1097-2765(00)80269-5

実験手法

X-RAY DIFFRACTION (1.7 Å)