2q13

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==Overview==
==Overview==
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APPL1 is an effector of the small GTPase Rab5. Together, they mediate a, signal transduction pathway initiated by ligand binding to cell surface, receptors. Interaction with Rab5 is confined to the amino (N)-terminal, region of APPL1. We report the crystal structures of human APPL1, N-terminal BAR-PH domain motif. The BAR and PH domains, together with a, novel linker helix, form an integrated, crescent-shaped, symmetrical, dimer. This BAR-PH interaction is likely conserved in the class of BAR-PH, containing proteins. Biochemical analyses indicate two independent, Rab-binding sites located at the opposite ends of the dimer, where the PH, domain directly interacts with Rab5 and Rab21. Besides structurally, supporting the PH domain, the BAR domain also contributes to Rab binding, through a small surface region in the vicinity of the PH domain. In stark, contrast to the helix-dominated, Rab-binding domains previously reported, APPL1 PH domain employs beta-strands to interact with Rab5. On the Rab5, side, both switch regions are involved in the interaction. Thus we, identified a new binding mode between PH domains and small GTPases.
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APPL1 is an effector of the small GTPase Rab5. Together, they mediate a signal transduction pathway initiated by ligand binding to cell surface receptors. Interaction with Rab5 is confined to the amino (N)-terminal region of APPL1. We report the crystal structures of human APPL1 N-terminal BAR-PH domain motif. The BAR and PH domains, together with a novel linker helix, form an integrated, crescent-shaped, symmetrical dimer. This BAR-PH interaction is likely conserved in the class of BAR-PH containing proteins. Biochemical analyses indicate two independent Rab-binding sites located at the opposite ends of the dimer, where the PH domain directly interacts with Rab5 and Rab21. Besides structurally supporting the PH domain, the BAR domain also contributes to Rab binding through a small surface region in the vicinity of the PH domain. In stark contrast to the helix-dominated, Rab-binding domains previously reported, APPL1 PH domain employs beta-strands to interact with Rab5. On the Rab5 side, both switch regions are involved in the interaction. Thus we identified a new binding mode between PH domains and small GTPases.
==About this Structure==
==About this Structure==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Zhang, X.C.]]
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[[Category: Zhang, X C.]]
[[Category: Zhu, G.]]
[[Category: Zhu, G.]]
[[Category: appl1]]
[[Category: appl1]]
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[[Category: protein transport]]
[[Category: protein transport]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:12:57 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:34:56 2008''

Revision as of 16:34, 21 February 2008


2q13, resolution 2.05Å

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Crystal structure of BAR-PH domain of APPL1

Overview

APPL1 is an effector of the small GTPase Rab5. Together, they mediate a signal transduction pathway initiated by ligand binding to cell surface receptors. Interaction with Rab5 is confined to the amino (N)-terminal region of APPL1. We report the crystal structures of human APPL1 N-terminal BAR-PH domain motif. The BAR and PH domains, together with a novel linker helix, form an integrated, crescent-shaped, symmetrical dimer. This BAR-PH interaction is likely conserved in the class of BAR-PH containing proteins. Biochemical analyses indicate two independent Rab-binding sites located at the opposite ends of the dimer, where the PH domain directly interacts with Rab5 and Rab21. Besides structurally supporting the PH domain, the BAR domain also contributes to Rab binding through a small surface region in the vicinity of the PH domain. In stark contrast to the helix-dominated, Rab-binding domains previously reported, APPL1 PH domain employs beta-strands to interact with Rab5. On the Rab5 side, both switch regions are involved in the interaction. Thus we identified a new binding mode between PH domains and small GTPases.

About this Structure

2Q13 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the APPL1 BAR-PH domain and characterization of its interaction with Rab5., Zhu G, Chen J, Liu J, Brunzelle JS, Huang B, Wakeham N, Terzyan S, Li X, Rao Z, Li G, Zhang XC, EMBO J. 2007 Jul 25;26(14):3484-93. Epub 2007 Jun 21. PMID:17581628

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