3vlc

Crystal structure of S. cerevisiae Get3 in the semi open conformation in complex with Get1 cytosolic domain at 4.5 angstrom resolutionCrystal structure of S. cerevisiae Get3 in the semi open conformation in complex with Get1 cytosolic domain at 4.5 angstrom resolution

Structural highlights

3vlc is a 2 chain structure with sequence from Saccharomyces cerevisiae and Saccharomyces cerevisiae s288c. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	GET1, MDM39, YGL020C (Saccharomyces cerevisiae S288c)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[GET1_YEAST] Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Together with GET2, acts as a membrane receptor for soluble GET3, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. The GET complex cooperates with the HDEL receptor ERD2 to mediate the ATP-dependent retrieval of resident ER proteins that contain a C-terminal H-D-E-L retention signal from the Golgi to the ER. Involved in mitochondrial distribution and morphology.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Tail-anchored (TA) proteins are integral membrane proteins that possess a single transmembrane domain near their carboxy terminus. TA proteins play critical roles in many important cellular processes such as membrane trafficking, protein translocation, and apoptosis. The GET complex mediates posttranslational insertion of newly synthesized TA proteins to the endoplasmic reticulum membrane. The GET complex is composed of the homodimeric Get3 ATPase and its heterooligomeric receptor, Get1/2. During insertion, the Get3 dimer shuttles between open and closed conformational states, coupled with ATP hydrolysis and the binding/release of TA proteins. We report crystal structures of ADP-bound Get3 in complex with the cytoplasmic domain of Get1 (Get1CD) in open and semi-open conformations at 3.0- and 4.5-A resolutions, respectively. Our structures and biochemical data suggest that Get1 uses two interfaces to stabilize the open dimer conformation of Get3. We propose that one interface is sufficient for binding of Get1 by Get3, while the second interface stabilizes the open dimer conformation of Get3.

Get1 Stabilizes an Open Dimer Conformation of Get3 ATPase by Binding Two Distinct Interfaces.,Kubota K, Yamagata A, Sato Y, Goto-Ito S, Fukai S J Mol Biol. 2012 Jun 7. PMID:22684149^[6]

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

References

↑ Dimmer KS, Fritz S, Fuchs F, Messerschmitt M, Weinbach N, Neupert W, Westermann B. Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol Biol Cell. 2002 Mar;13(3):847-53. PMID:11907266 doi:10.1091/mbc.01-12-0588
↑ Schuldiner M, Collins SR, Thompson NJ, Denic V, Bhamidipati A, Punna T, Ihmels J, Andrews B, Boone C, Greenblatt JF, Weissman JS, Krogan NJ. Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell. 2005 Nov 4;123(3):507-19. PMID:16269340 doi:S0092-8674(05)00868-8
↑ Schuldiner M, Metz J, Schmid V, Denic V, Rakwalska M, Schmitt HD, Schwappach B, Weissman JS. The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell. 2008 Aug 22;134(4):634-45. PMID:18724936 doi:S0092-8674(08)00777-0
↑ Wang F, Whynot A, Tung M, Denic V. The mechanism of tail-anchored protein insertion into the ER membrane. Mol Cell. 2011 Sep 2;43(5):738-50. doi: 10.1016/j.molcel.2011.07.020. Epub 2011, Aug 11. PMID:21835666 doi:10.1016/j.molcel.2011.07.020
↑ Stefer S, Reitz S, Wang F, Wild K, Pang YY, Schwarz D, Bomke J, Hein C, Lohr F, Bernhard F, Denic V, Dotsch V, Sinning I. Structural Basis for Tail-Anchored Membrane Protein Biogenesis by the Get3-Receptor Complex. Science. 2011 Jun 30. PMID:21719644 doi:10.1126/science.1207125
↑ Kubota K, Yamagata A, Sato Y, Goto-Ito S, Fukai S. Get1 Stabilizes an Open Dimer Conformation of Get3 ATPase by Binding Two Distinct Interfaces. J Mol Biol. 2012 Jun 7. PMID:22684149 doi:10.1016/j.jmb.2012.05.045

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OCA

[1] Dimmer KS, Fritz S, Fuchs F, Messerschmitt M, Weinbach N, Neupert W, Westermann B. Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol Biol Cell. 2002 Mar;13(3):847-53. PMID:11907266 doi:10.1091/mbc.01-12-0588

[2] Schuldiner M, Collins SR, Thompson NJ, Denic V, Bhamidipati A, Punna T, Ihmels J, Andrews B, Boone C, Greenblatt JF, Weissman JS, Krogan NJ. Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell. 2005 Nov 4;123(3):507-19. PMID:16269340 doi:S0092-8674(05)00868-8

[3] Schuldiner M, Metz J, Schmid V, Denic V, Rakwalska M, Schmitt HD, Schwappach B, Weissman JS. The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell. 2008 Aug 22;134(4):634-45. PMID:18724936 doi:S0092-8674(08)00777-0

[4] Wang F, Whynot A, Tung M, Denic V. The mechanism of tail-anchored protein insertion into the ER membrane. Mol Cell. 2011 Sep 2;43(5):738-50. doi: 10.1016/j.molcel.2011.07.020. Epub 2011, Aug 11. PMID:21835666 doi:10.1016/j.molcel.2011.07.020

[5] Stefer S, Reitz S, Wang F, Wild K, Pang YY, Schwarz D, Bomke J, Hein C, Lohr F, Bernhard F, Denic V, Dotsch V, Sinning I. Structural Basis for Tail-Anchored Membrane Protein Biogenesis by the Get3-Receptor Complex. Science. 2011 Jun 30. PMID:21719644 doi:10.1126/science.1207125

[6] Kubota K, Yamagata A, Sato Y, Goto-Ito S, Fukai S. Get1 Stabilizes an Open Dimer Conformation of Get3 ATPase by Binding Two Distinct Interfaces. J Mol Biol. 2012 Jun 7. PMID:22684149 doi:10.1016/j.jmb.2012.05.045

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