FHA 结构域的磷酸化非依赖性双位点结合介导 centaurin alpha1 对磷酸肌醇的转运
Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1.
机构信息
Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
出版信息
Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20346-51. doi: 10.1073/pnas.1009008107. Epub 2010 Nov 5.
Abstract
Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin α1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)P(2)). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule.
摘要
磷脂酰肌醇 3,4,5-三磷酸（PIP3）在神经元极化和轴突形成中起着关键作用。通过衔接蛋白 centaurin α1（CENTA1），含有 PIP3 的囊泡被运送到轴突末端的驱动蛋白 KIF13B。KIF13B 通过其与叉头相关（FHA）结构域与 CENTA1 相互作用。我们解析了无配体、KIF13B-FHA 结构域结合、以及 PIP3 头部基团（IP4）结合构象的 CENTA1 的晶体结构，以及 CENTA1/KIF13B-FHA/IP4 三元复合物的晶体结构。CENTA1 的第一个pleckstrin 同源（PH）结构域特异性结合 PIP3，而第二个 PH 结构域同时结合 PIP3 和磷脂酰肌醇 3,4-二磷酸（PI(3,4)P(2)）。KIF13B 的 FHA 结构域以一种不依赖于苏氨酸磷酸化的方式与一个 CENTA1 分子的 PH1 结构域和第二个 CENTA1 分子的 ArfGAP 结构域相互作用。我们提出全长 KIF13B 和 CENTA1 形成异四聚体，能够在囊泡中结合四个磷酸肌醇分子，并沿着微管运输囊泡。
相似文献
1
Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1.FHA 结构域的磷酸化非依赖性双位点结合介导 centaurin alpha1 对磷酸肌醇的转运
Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20346-51. doi: 10.1073/pnas.1009008107. Epub 2010 Nov 5.
2
Centaurin-alpha1 interacts directly with kinesin motor protein KIF13B.CENTAURIN-α1与驱动蛋白运动蛋白KIF13B直接相互作用。
J Cell Sci. 2005 Jun 1;118(Pt 11):2471-84. doi: 10.1242/jcs.02369.
3
In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1.体外重建揭示了磷酯酰肌醇作为货物释放因子和 ARF6 GAP ADAP1 的激活剂。
Proc Natl Acad Sci U S A. 2021 Jan 5;118(1). doi: 10.1073/pnas.2010054118. Epub 2020 Dec 18.
4
Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity.驱动蛋白-3家族蛋白GAKIN对磷脂酰肌醇-3,4,5-三磷酸（PIP3）的转运调节神经元细胞极性。
J Cell Biol. 2006 Jul 31;174(3):425-36. doi: 10.1083/jcb.200604031. Epub 2006 Jul 24.
5
Centaurin-alpha1 and KIF13B kinesin motor protein interaction in ARF6 signalling.在ARF6信号传导中，Centaurin-α1与驱动蛋白KIF13B的相互作用
Biochem Soc Trans. 2005 Dec;33(Pt 6):1279-81. doi: 10.1042/BST0331279.
6
Functions of the neuron-specific protein ADAP1 (centaurin-α1) in neuronal differentiation and neurodegenerative diseases, with an overview of structural and biochemical properties of ADAP1.神经元特异性蛋白ADAP1（centaurin-α1）在神经元分化和神经退行性疾病中的作用，以及ADAP1的结构和生化特性概述。
Biol Chem. 2014 Nov 1;395(11):1321-40. doi: 10.1515/hsz-2014-0107.
7
p42(IP4)/centaurin alpha1, a brain-specific PtdIns(3,4,5)P3/Ins(1,3,4,5)P4-binding protein: membrane trafficking induced by epidermal growth factor is inhibited by stimulation of phospholipase C-coupled thrombin receptor.p42（IP4）/centaurin α1，一种脑特异性磷脂酰肌醇（3,4,5）三磷酸/肌醇（1,3,4,5）四磷酸结合蛋白：表皮生长因子诱导的膜运输受到磷脂酶C偶联的凝血酶受体刺激的抑制。
Neurochem Res. 2005 Oct;30(10):1319-30. doi: 10.1007/s11064-005-8804-1.
8
Interaction of the brain-specific protein p42IP4/centaurin-alpha1 with the peptidase nardilysin is regulated by the cognate ligands of p42IP4, PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4, with stereospecificity.脑特异性蛋白p42IP4/centaurin-α1与肽酶nardilysin的相互作用受p42IP4的同源配体PtdIns(3,4,5)P3和Ins(1,3,4,5)P4的立体特异性调节。
J Neurochem. 2006 Jul;98(2):343-54. doi: 10.1111/j.1471-4159.2006.03869.x.
9
Centaurin-alpha1 is an in vivo phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein for ARF6 that is involved in actin cytoskeleton organization.CENTAURIN-α1是一种体内磷脂酰肌醇3,4,5-三磷酸依赖性GTP酶激活蛋白，作用于ARF6，参与肌动蛋白细胞骨架的组织。
J Biol Chem. 2004 Feb 20;279(8):6205-8. doi: 10.1074/jbc.C300482200. Epub 2003 Nov 18.
10
Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation.Par1b/MARK2 通过磷酸化驱动蛋白样马达蛋白 GAKIN/KIF13B 来调节轴突形成。
Mol Cell Biol. 2010 May;30(9):2206-19. doi: 10.1128/MCB.01181-09. Epub 2010 Mar 1.
引用本文的文献
1
Mechanism and regulation of kinesin motors.驱动蛋白的作用机制与调控
Nat Rev Mol Cell Biol. 2025 Feb;26(2):86-103. doi: 10.1038/s41580-024-00780-6. Epub 2024 Oct 11.
2
Specific kinesin and dynein molecules participate in the unconventional protein secretion of transmembrane proteins.特定的驱动蛋白和动力蛋白分子参与跨膜蛋白的非常规蛋白质分泌。
Korean J Physiol Pharmacol. 2024 Sep 1;28(5):435-447. doi: 10.4196/kjpp.2024.28.5.435.
3
Polarized transport requires AP-1-mediated recruitment of KIF13A and KIF13B at the trans-Golgi.极化运输需要 AP-1 介导的 KIF13A 和 KIF13B 在反式高尔基体的募集。
Mol Biol Cell. 2024 May 1;35(5):ar61. doi: 10.1091/mbc.E23-10-0401. Epub 2024 Mar 6.
4
Control of motor landing and processivity by the CAP-Gly domain in the KIF13B tail.CAP-Gly 结构域控制 KIF13B 尾部的马达着陆和进程性。
Nat Commun. 2023 Aug 5;14(1):4715. doi: 10.1038/s41467-023-40425-4.
5
The role of forkhead-associated (FHA)-domain proteins in plant biology.叉头相关（FHA）结构域蛋白在植物生物学中的作用。
Plant Mol Biol. 2023 Apr;111(6):455-472. doi: 10.1007/s11103-023-01338-4. Epub 2023 Feb 28.
6
Functional Role of AGAP2/PIKE-A in Fcγ Receptor-Mediated Phagocytosis.AGAP2/PIKE-A 在 Fcγ 受体介导的吞噬作用中的功能作用。
Cells. 2022 Dec 24;12(1):72. doi: 10.3390/cells12010072.
7
Afadin couples RAS GTPases to the polarity rheostat Scribble.Afadin 将 RAS GTPases 与极性变阻器 Scribble 偶联。
Nat Commun. 2022 Aug 5;13(1):4562. doi: 10.1038/s41467-022-32335-8.
8
Phosphoregulation of Kinesins Involved in Long-Range Intracellular Transport.参与长距离细胞内运输的驱动蛋白的磷酸化调控
Front Cell Dev Biol. 2022 Jun 3;10:873164. doi: 10.3389/fcell.2022.873164. eCollection 2022.
9
ADAP1 promotes latent HIV-1 reactivation by selectively tuning KRAS-ERK-AP-1 T cell signaling-transcriptional axis.ADAP1 通过选择性调节 KRAS-ERK-AP-1 T 细胞信号转导-转录轴促进潜伏 HIV-1 的重新激活。
Nat Commun. 2022 Mar 1;13(1):1109. doi: 10.1038/s41467-022-28772-0.
10
A novel approach in preventing vascular leakage and angiogenesis in wet age-related macular degeneration.一种预防湿性年龄相关性黄斑变性中血管渗漏和血管生成的新方法。
Neural Regen Res. 2022 Aug;17(8):1751-1752. doi: 10.4103/1673-5374.332147.
本文引用的文献
1
The mechanisms of kinesin motor motility: lessons from the monomeric motor KIF1A.驱动蛋白运动机制：来自单体驱动蛋白KIF1A的经验教训。
Nat Rev Mol Cell Biol. 2009 Dec;10(12):877-84. doi: 10.1038/nrm2807.
2
The ATPase cycle of the mitotic motor CENP-E.有丝分裂动力蛋白CENP-E的ATP酶循环
J Biol Chem. 2009 Nov 20;284(47):32858-68. doi: 10.1074/jbc.M109.041210. Epub 2009 Sep 16.
3
Walking the walk: how kinesin and dynein coordinate their steps.身体力行：驱动蛋白与动力蛋白如何协调它们的步伐。
Curr Opin Cell Biol. 2009 Feb;21(1):59-67. doi: 10.1016/j.ceb.2008.12.002. Epub 2009 Jan 27.
4
Structure and function of the phosphothreonine-specific FHA domain.磷酸苏氨酸特异性FHA结构域的结构与功能。
Sci Signal. 2008 Dec 23;1(51):re12. doi: 10.1126/scisignal.151re12.
5
Capturing protein tails by CAP-Gly domains.通过CAP-Gly结构域捕获蛋白质尾巴。
Trends Biochem Sci. 2008 Nov;33(11):535-45. doi: 10.1016/j.tibs.2008.08.006. Epub 2008 Oct 4.
6
Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin.驱动蛋白应变依赖性微管激活Mg-ADP释放的结构模型。
Nat Struct Mol Biol. 2008 Oct;15(10):1067-75. doi: 10.1038/nsmb.1487. Epub 2008 Sep 21.
7
Understanding PTEN regulation: PIP2, polarity and protein stability.了解PTEN调控：磷脂酰肌醇-4,5-二磷酸、极性与蛋白质稳定性。
Oncogene. 2008 Sep 18;27(41):5464-76. doi: 10.1038/onc.2008.243.
8
Mechanistic insights into phosphoprotein-binding FHA domains.对磷蛋白结合FHA结构域的机制性见解。
Acc Chem Res. 2008 Aug;41(8):991-9. doi: 10.1021/ar700148u. Epub 2008 Jul 26.
9
Membrane recognition by phospholipid-binding domains.磷脂结合结构域对膜的识别
Nat Rev Mol Cell Biol. 2008 Feb;9(2):99-111. doi: 10.1038/nrm2328.
10
The effector domain of human Dlg tumor suppressor acts as a switch that relieves autoinhibition of kinesin-3 motor GAKIN/KIF13B.人类Dlg肿瘤抑制因子的效应结构域充当一种开关，可解除驱动蛋白-3马达GAKIN/KIF13B的自身抑制。
Biochemistry. 2007 Sep 4;46(35):10039-45. doi: 10.1021/bi701169w. Epub 2007 Aug 14.
Zotero 插件