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4c0a

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Revision as of 13:42, 13 March 2019

Arf1(Delta1-17)in complex with BRAG2 Sec7-PH domain

Structural highlights

4c0a is a 8 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IQEC1_HUMAN] In addition to accelerate GTP gamma S binding by ARFs of all three classes, it appears to function preferentially as a guanine nucleotide exchange protein for ARF6, mediating internalisation of beta-1 integrin.^[1] ^[2] [ARF1_BOVIN] GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles.

Publication Abstract from PubMed

The mechanisms whereby guanine nucleotide exchange factors (GEFs) coordinate their subcellular targeting to their activation of small GTPases remain poorly understood. Here we analyzed how membranes control the efficiency of human BRAG2, an ArfGEF involved in receptor endocytosis, Wnt signaling, and tumor invasion. The crystal structure of an Arf1-BRAG2 complex that mimics a membrane-bound intermediate revealed an atypical PH domain that is constitutively anchored to the catalytic Sec7 domain and interacts with Arf. Combined with the quantitative analysis of BRAG2 exchange activity reconstituted on membranes, we find that this PH domain potentiates nucleotide exchange by about 2,000-fold by cumulative conformational and membrane-targeting contributions. Furthermore, it restricts BRAG2 activity to negatively charged membranes without phosphoinositide specificity, using a positively charged surface peripheral to but excluding the canonical lipid-binding pocket. This suggests a model of BRAG2 regulation along the early endosomal pathway that expands the repertoire of GEF regulatory mechanisms. Notably, it departs from the auto-inhibitory and feedback loop paradigm emerging from studies of SOS and cytohesins. It also uncovers a novel mechanism of unspecific lipid-sensing by PH domains that may allow sustained binding to maturating membranes.

Integrated Conformational and Lipid-Sensing Regulation of Endosomal ArfGEF BRAG2.,Aizel K, Biou V, Navaza J, Duarte LV, Campanacci V, Cherfils J, Zeghouf M PLoS Biol. 2013 Sep;11(9):e1001652. doi: 10.1371/journal.pbio.1001652. Epub 2013 , Sep 10. PMID:24058294^[3]

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

References

↑ Someya A, Sata M, Takeda K, Pacheco-Rodriguez G, Ferrans VJ, Moss J, Vaughan M. ARF-GEP(100), a guanine nucleotide-exchange protein for ADP-ribosylation factor 6. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2413-8. PMID:11226253 doi:http://dx.doi.org/10.1073/pnas.051634798
↑ Dunphy JL, Moravec R, Ly K, Lasell TK, Melancon P, Casanova JE. The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta1 integrins. Curr Biol. 2006 Feb 7;16(3):315-20. PMID:16461286 doi:http://dx.doi.org/10.1016/j.cub.2005.12.032
↑ Aizel K, Biou V, Navaza J, Duarte LV, Campanacci V, Cherfils J, Zeghouf M. Integrated Conformational and Lipid-Sensing Regulation of Endosomal ArfGEF BRAG2. PLoS Biol. 2013 Sep;11(9):e1001652. doi: 10.1371/journal.pbio.1001652. Epub 2013 , Sep 10. PMID:24058294 doi:10.1371/journal.pbio.1001652

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4c0a"

@@ Line 1: / Line 1: @@
 ==Arf1(Delta1-17)in complex with BRAG2 Sec7-PH domain==
-<StructureSection load='4c0a' size='340' side='right' caption='[[4c0a]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+<StructureSection load='4c0a' size='340' side='right'caption='[[4c0a]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4c0a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C0A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C0A FirstGlance]. <br>
@@ Line 24: / Line 24: @@
 [[Category: Bovin]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Aizel, K]]
 [[Category: Biou, V]]

4c0a

From Proteopedia

Revision as of 13:42, 13 March 2019

Arf1(Delta1-17)in complex with BRAG2 Sec7-PH domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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