FYVE结构域对磷脂酰肌醇3-磷酸的识别

Phosphatidylinositol 3-phosphate recognition by the FYVE domain.

作者信息

Kutateladze T G, Ogburn K D, Watson W T, de Beer T, Emr S D, Burd C G, Overduin M

机构信息

Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.

出版信息

Mol Cell. 1999 Jun;3(6):805-11. doi: 10.1016/s1097-2765(01)80013-7.

DOI:10.1016/s1097-2765(01)80013-7

PMID:10394369

Abstract

Recognition of phosphatidylinositol 3-phosphate (Ptdlns(3)P) is crucial for a broad range of cellular signaling and membrane trafficking events regulated by phosphoinositide (PI) 3-kinases. PtdIns(3)P binding by the FYVE domain of human early endosome autoantigen 1 (EEA1), a protein implicated in endosome fusion, involves two beta hairpins and an alpha helix. Specific amino acids, including those of the FYVE domain's conserved RRHHCRQCGNIF motif, contact soluble and micelle-embedded lipid and provide specificity for Ptdlns(3)P over Ptdlns(5)P and Ptdlns, as shown by heteronuclear magnetic resonance spectroscopy. Although the FYVE domain relies on a zinc-binding motif reminiscent of RING fingers, it is distinguished by ovel structural features and its ptdlns(3)P-binding site.

摘要

对磷脂酰肌醇3-磷酸（Ptdlns(3)P）的识别对于由磷酸肌醇（PI）3-激酶调节的广泛细胞信号传导和膜运输事件至关重要。人早期内体自身抗原1（EEA1）的FYVE结构域与PtdIns(3)P结合，EEA1是一种参与内体融合的蛋白质，该结合涉及两个β发夹和一个α螺旋。特定氨基酸，包括FYVE结构域保守的RRHHCRQCGNIF基序中的氨基酸，与可溶性和嵌入胶束的脂质接触，并赋予Ptdlns(3)P相对于Ptdlns(5)P和Ptdlns的特异性，如异核磁共振波谱所示。尽管FYVE结构域依赖于类似于RING指结构的锌结合基序，但其独特的结构特征和Ptdlns(3)P结合位点使其与众不同。