1U2B

Triglycine variant of the Grp1 Pleckstrin Homology Domain unliganded

1U2B の概要

• エントリーDOI: 10.2210/pdb1u2b/pdb
• 関連するPDBエントリー: 1U27 1U29
• 分子名称: Cytohesin 3, SULFATE ION (3 entities in total)
• 機能のキーワード: ph domain, lipid binding, phosphoinositides, lipid binding protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cell membrane (By similarity): O08967
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16451.57

構造登録者

Cronin, T.C.,DiNitto, J.P.,Czech, M.P.,Lambright, D.G. (登録日: 2004-07-16, 公開日: 2005-02-01, 最終更新日: 2023-08-23)

主引用文献

Cronin, T.C.,DiNitto, J.P.,Czech, M.P.,Lambright, D.G.
Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains
Embo J., 23:3711-3720, 2004

PubMed Abstract: The pleckstrin homology (PH) domains of the homologous proteins Grp1 (general receptor for phosphoinositides), ARNO (Arf nucleotide binding site opener), and Cytohesin-1 bind phosphatidylinositol (PtdIns) 3,4,5-trisphosphate with unusually high selectivity. Remarkably, splice variants that differ only by the insertion of a single glycine residue in the beta1/beta2 loop exhibit dual specificity for PtdIns(3,4,5)P(3) and PtdIns(4,5)P(2). The structural basis for this dramatic specificity switch is not apparent from the known modes of phosphoinositide recognition. Here, we report crystal structures for dual specificity variants of the Grp1 and ARNO PH domains in either the unliganded form or in complex with the head groups of PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3). Loss of contacts with the beta1/beta2 loop with no significant change in head group orientation accounts for the significant decrease in PtdIns(3,4,5)P(3) affinity observed for the dual specificity variants. Conversely, a small increase rather than decrease in affinity for PtdIns(4,5)P(2) is explained by a novel binding mode, in which the glycine insertion alleviates unfavorable interactions with the beta1/beta2 loop. These observations are supported by a systematic mutational analysis of the determinants of phosphoinositide recognition.

PubMed: 15359279
DOI: 10.1038/sj.emboj.7600388

実験手法

X-RAY DIFFRACTION (1.8 Å)