3ftq

From Proteopedia

(Difference between revisions)

Revision as of 05:53, 25 December 2014

Crystal structure of Septin 2 in complex with GppNHp and Mg2+

Structural highlights

3ftq is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	Sept2, Nedd-5, Nedd5 (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[SEPT2_MOUSE] Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium by maintaining polyglutamylated microtubules, thus facilitating efficient vesicle transport, and by impeding MAP4 binding to tubulin. Required for the progression through mitosis. Forms a scaffold at the midplane of the mitotic splindle required to maintain CENPE localization at kinetochores and consequently chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements (By similarity). In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes: probably acts by regulating the assembly of the tectonic-like complex (also named B9 complex) by localizing TMEM231 protein.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Septins constitute a group of GTP-binding proteins involved in cytokinesis and other essential cellular functions. They form heterooligomeric complexes that polymerize into nonpolar filaments and are dynamic during different stages of the cell cycle. Posttranslational modifications and interacting partners are widely accepted regulators of septin filament function, but the contribution of nucleotide is undefined due to a lack of detailed structural information. Previous low-resolution structures showed that the G domain assembles into a linear polymer with 2 different interfaces involving the N and C termini and the G binding sites. Here we report the crystal structure of SEPT2 bound to GppNHp at 2.9 A resolution. GTP binding induces conformational changes in the switch regions at the G interfaces, which are transmitted to the N-terminal helix and also affect the NC interface. Biochemical studies and sequence alignment suggest that a threonine, which is conserved in certain subgroups of septins, is responsible for GTP hydrolysis. Although this threonine is not present in yeast CDC3 and CDC11, its mutation in CDC10 and CDC12 induces temperature sensitivity. Highly conserved contact residues identified in the G interface are shown to be necessary for Cdc3-10, but not Cdc11-12, heterodimer formation and cell growth in yeast. Based on our findings, we propose that GTP binding/hydrolysis and the nature of the nucleotide influence the stability of interfaces in heterooligomeric and polymeric septins and are required for proper septin filament assembly/disassembly. These data also offer a first rationale for subdividing human septins into different functional subgroups.

GTP-induced conformational changes in septins and implications for function.,Sirajuddin M, Farkasovsky M, Zent E, Wittinghofer A Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16592-7. Epub 2009 Sep 15. PMID:19805342^[4]

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

References

↑ Kinoshita M, Kumar S, Mizoguchi A, Ide C, Kinoshita A, Haraguchi T, Hiraoka Y, Noda M. Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures. Genes Dev. 1997 Jun 15;11(12):1535-47. PMID:9203580
↑ Hu Q, Milenkovic L, Jin H, Scott MP, Nachury MV, Spiliotis ET, Nelson WJ. A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science. 2010 Jul 23;329(5990):436-9. doi: 10.1126/science.1191054. Epub 2010 Jun, 17. PMID:20558667 doi:http://dx.doi.org/10.1126/science.1191054
↑ Chih B, Liu P, Chinn Y, Chalouni C, Komuves LG, Hass PE, Sandoval W, Peterson AS. A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nat Cell Biol. 2011 Dec 18;14(1):61-72. doi: 10.1038/ncb2410. PMID:22179047 doi:http://dx.doi.org/10.1038/ncb2410
↑ Sirajuddin M, Farkasovsky M, Zent E, Wittinghofer A. GTP-induced conformational changes in septins and implications for function. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16592-7. Epub 2009 Sep 15. PMID:19805342

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ftq"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ftq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ftq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ftq RCSB], [http://www.ebi.ac.uk/pdbsum/3ftq PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SEPT2_MOUSE SEPT2_MOUSE]] Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium by maintaining polyglutamylated microtubules, thus facilitating efficient vesicle transport, and by impeding MAP4 binding to tubulin. Required for the progression through mitosis. Forms a scaffold at the midplane of the mitotic splindle required to maintain CENPE localization at kinetochores and consequently chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements (By similarity). In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes: probably acts by regulating the assembly of the tectonic-like complex (also named B9 complex) by localizing TMEM231 protein.<ref>PMID:9203580</ref> <ref>PMID:20558667</ref> <ref>PMID:22179047</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3ftq

From Proteopedia

Revision as of 05:53, 25 December 2014

Crystal structure of Septin 2 in complex with GppNHp and Mg2+

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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