6if3: Difference between revisions

Latest revision as of 09:40, 22 November 2023

Complex structure of Rab35 and its effector ACAP2

Structural highlights

6if3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:	GTP, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACAP2_HUMAN GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6).^[1]

Publication Abstract from PubMed

Rab35, a master regulator of membrane trafficking, regulates diverse cellular processes and is associated with various human diseases. Although a number of effectors have been identified, the molecular basis of Rab35-effector interactions remains unclear. Here, we provide the high-resolution crystal structures of Rab35 in complex with its two specific effectors ACAP2 and RUSC2, respectively. In the Rab35/ACAP2 complex structure, Rab35 binds to the terminal ankyrin repeat and a C-terminal extended alpha helix of ACAP2, revealing a previously uncharacterized binding mode both for Rabs and ankyrin repeats. In the Rab35/RUSC2 complex structure, Arg1015 of RUSC2 functions as a "pseudo-arginine finger" that stabilizes the GTP-bound Rab35, thus facilitating the assembly of Rab35/RUSC2 complex. The structural analysis allows us to design specific Rab35 mutants capable of eliminating Rab35/ACAP2 and Rab35/RUSC2 interactions, but not interfering with other effector bindings. The atomic structures also offer possible explanations to disease-associated mutants identified at the Rab35-effector interfaces.

Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase.,Lin L, Shi Y, Wang M, Wang C, Zhu J, Zhang R Structure. 2019 Mar 11. pii: S0969-2126(19)30078-4. doi:, 10.1016/j.str.2019.02.008. PMID:30905672^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jackson TR, Brown FD, Nie Z, Miura K, Foroni L, Sun J, Hsu VW, Donaldson JG, Randazzo PA. ACAPs are arf6 GTPase-activating proteins that function in the cell periphery. J Cell Biol. 2000 Oct 30;151(3):627-38. PMID:11062263
↑ Lin L, Shi Y, Wang M, Wang C, Zhu J, Zhang R. Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase. Structure. 2019 Mar 11. pii: S0969-2126(19)30078-4. doi:, 10.1016/j.str.2019.02.008. PMID:30905672 doi:https://dx.doi.org/10.1016/j.str.2019.02.008

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Jackson TR, Brown FD, Nie Z, Miura K, Foroni L, Sun J, Hsu VW, Donaldson JG, Randazzo PA. ACAPs are arf6 GTPase-activating proteins that function in the cell periphery. J Cell Biol. 2000 Oct 30;151(3):627-38. PMID:11062263

[2] Lin L, Shi Y, Wang M, Wang C, Zhu J, Zhang R. Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase. Structure. 2019 Mar 11. pii: S0969-2126(19)30078-4. doi:, 10.1016/j.str.2019.02.008. PMID:30905672 doi:https://dx.doi.org/10.1016/j.str.2019.02.008

[1]

[2]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6if3 is ON HOLD
+==Complex structure of Rab35 and its effector ACAP2==
+<StructureSection load='6if3' size='340' side='right'caption='[[6if3]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6if3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IF3 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6if3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6if3 OCA], [https://pdbe.org/6if3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6if3 RCSB], [https://www.ebi.ac.uk/pdbsum/6if3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6if3 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ACAP2_HUMAN ACAP2_HUMAN] GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6).<ref>PMID:11062263</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Rab35, a master regulator of membrane trafficking, regulates diverse cellular processes and is associated with various human diseases. Although a number of effectors have been identified, the molecular basis of Rab35-effector interactions remains unclear. Here, we provide the high-resolution crystal structures of Rab35 in complex with its two specific effectors ACAP2 and RUSC2, respectively. In the Rab35/ACAP2 complex structure, Rab35 binds to the terminal ankyrin repeat and a C-terminal extended alpha helix of ACAP2, revealing a previously uncharacterized binding mode both for Rabs and ankyrin repeats. In the Rab35/RUSC2 complex structure, Arg1015 of RUSC2 functions as a "pseudo-arginine finger" that stabilizes the GTP-bound Rab35, thus facilitating the assembly of Rab35/RUSC2 complex. The structural analysis allows us to design specific Rab35 mutants capable of eliminating Rab35/ACAP2 and Rab35/RUSC2 interactions, but not interfering with other effector bindings. The atomic structures also offer possible explanations to disease-associated mutants identified at the Rab35-effector interfaces.
-Authors: Lin, L., Jinwei, Z., Rongguang, z.
+Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase.,Lin L, Shi Y, Wang M, Wang C, Zhu J, Zhang R Structure. 2019 Mar 11. pii: S0969-2126(19)30078-4. doi:, 10.1016/j.str.2019.02.008. PMID:30905672<ref>PMID:30905672</ref>
-Description: Complex structure of Rab35 and its effector ACAP2
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lin, L]]
+<div class="pdbe-citations 6if3" style="background-color:#fffaf0;"></div>
-[[Category: Rongguang, Z]]
-[[Category: Jinwei, Z]]
+==See Also==
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
+*[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Lin L]]
+[[Category: Zhang R]]
+[[Category: Zhu J]]

6if3: Difference between revisions

Latest revision as of 09:40, 22 November 2023

Complex structure of Rab35 and its effector ACAP2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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