1z0a: Difference between revisions

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New page: left|200px<br /> <applet load="1z0a" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z0a, resolution 2.12Å" /> '''GDP-Bound Rab2A GTP...
 
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[[Image:1z0a.gif|left|200px]]<br />
[[Image:1z0a.gif|left|200px]]<br /><applet load="1z0a" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="1z0a" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="1z0a, resolution 2.12&Aring;" />
caption="1z0a, resolution 2.12&Aring;" />
'''GDP-Bound Rab2A GTPase'''<br />
'''GDP-Bound Rab2A GTPase'''<br />


==Overview==
==Overview==
Rab GTPases regulate all stages of membrane trafficking, including vesicle, budding, cargo sorting, transport, tethering and fusion. In the inactive, (GDP-bound) conformation, accessory factors facilitate the targeting of, Rab GTPases to intracellular compartments. After nucleotide exchange to, the active (GTP-bound) conformation, Rab GTPases interact with, functionally diverse effectors including lipid kinases, motor proteins and, tethering complexes. How effectors distinguish between homologous Rab, GTPases represents an unresolved problem with respect to the specificity, of vesicular trafficking. Using a structural proteomic approach, we have, determined the specificity and structural basis underlying the interaction, of the multivalent effector rabenosyn-5 with the Rab family. The results, demonstrate that even the structurally similar effector domains in, rabenosyn-5 can achieve highly selective recognition of distinct subsets, of Rab GTPases exclusively through interactions with the switch and, interswitch regions. The observed specificity is determined at a, family-wide level by structural diversity in the active conformation, which governs the spatial disposition of critical conserved recognition, determinants, and by a small number of both positive and negative sequence, determinants that allow further discrimination between Rab GTPases with, similar switch conformations.
Rab GTPases regulate all stages of membrane trafficking, including vesicle budding, cargo sorting, transport, tethering and fusion. In the inactive (GDP-bound) conformation, accessory factors facilitate the targeting of Rab GTPases to intracellular compartments. After nucleotide exchange to the active (GTP-bound) conformation, Rab GTPases interact with functionally diverse effectors including lipid kinases, motor proteins and tethering complexes. How effectors distinguish between homologous Rab GTPases represents an unresolved problem with respect to the specificity of vesicular trafficking. Using a structural proteomic approach, we have determined the specificity and structural basis underlying the interaction of the multivalent effector rabenosyn-5 with the Rab family. The results demonstrate that even the structurally similar effector domains in rabenosyn-5 can achieve highly selective recognition of distinct subsets of Rab GTPases exclusively through interactions with the switch and interswitch regions. The observed specificity is determined at a family-wide level by structural diversity in the active conformation, which governs the spatial disposition of critical conserved recognition determinants, and by a small number of both positive and negative sequence determinants that allow further discrimination between Rab GTPases with similar switch conformations.


==Disease==
==Disease==
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==About this Structure==
==About this Structure==
1Z0A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Z0A OCA].  
1Z0A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z0A OCA].  


==Reference==
==Reference==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Eathiraj, S.]]
[[Category: Eathiraj, S.]]
[[Category: Lambright, D.G.]]
[[Category: Lambright, D G.]]
[[Category: Pan, X.]]
[[Category: Pan, X.]]
[[Category: Ritacco, C.]]
[[Category: Ritacco, C.]]
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[[Category: vesicular trafficking]]
[[Category: vesicular trafficking]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:27:55 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:53 2008''

Revision as of 17:10, 21 February 2008

File:1z0a.gif


1z0a, resolution 2.12Å

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GDP-Bound Rab2A GTPase

OverviewOverview

Rab GTPases regulate all stages of membrane trafficking, including vesicle budding, cargo sorting, transport, tethering and fusion. In the inactive (GDP-bound) conformation, accessory factors facilitate the targeting of Rab GTPases to intracellular compartments. After nucleotide exchange to the active (GTP-bound) conformation, Rab GTPases interact with functionally diverse effectors including lipid kinases, motor proteins and tethering complexes. How effectors distinguish between homologous Rab GTPases represents an unresolved problem with respect to the specificity of vesicular trafficking. Using a structural proteomic approach, we have determined the specificity and structural basis underlying the interaction of the multivalent effector rabenosyn-5 with the Rab family. The results demonstrate that even the structurally similar effector domains in rabenosyn-5 can achieve highly selective recognition of distinct subsets of Rab GTPases exclusively through interactions with the switch and interswitch regions. The observed specificity is determined at a family-wide level by structural diversity in the active conformation, which governs the spatial disposition of critical conserved recognition determinants, and by a small number of both positive and negative sequence determinants that allow further discrimination between Rab GTPases with similar switch conformations.

DiseaseDisease

Known disease associated with this structure: Carpenter syndrome OMIM:[606144]

About this StructureAbout this Structure

1Z0A is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis of family-wide Rab GTPase recognition by rabenosyn-5., Eathiraj S, Pan X, Ritacco C, Lambright DG, Nature. 2005 Jul 21;436(7049):415-9. PMID:16034420

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