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| | ==Coiled-coil oligomerization domain of the polycystin transient receptor potential channel PKD2L1== | | ==Coiled-coil oligomerization domain of the polycystin transient receptor potential channel PKD2L1== |
| | <StructureSection load='3te3' size='340' side='right' caption='[[3te3]], [[Resolution|resolution]] 2.69Å' scene=''> | | <StructureSection load='3te3' size='340' side='right' caption='[[3te3]], [[Resolution|resolution]] 2.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3te3]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TE3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TE3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3te3]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TE3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TE3 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKD2L1, PKD2L, PKDL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKD2L1, PKD2L, PKDL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <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=3te3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3te3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3te3 RCSB], [http://www.ebi.ac.uk/pdbsum/3te3 PDBsum]</span></td></tr> | + | <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=3te3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3te3 OCA], [http://pdbe.org/3te3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3te3 RCSB], [http://www.ebi.ac.uk/pdbsum/3te3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3te3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/PK2L1_HUMAN PK2L1_HUMAN]] Pore-forming subunit of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD1L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect.<ref>PMID:10517637</ref> <ref>PMID:19812697</ref> <ref>PMID:23212381</ref> <ref>PMID:24336289</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3te3" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Homo sapiens]] | + | [[Category: Human]] |
| | [[Category: Molland, K M]] | | [[Category: Molland, K M]] |
| | [[Category: Yernool, D A]] | | [[Category: Yernool, D A]] |
| Structural highlights
Function
[PK2L1_HUMAN] Pore-forming subunit of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD1L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect.[1] [2] [3] [4]
Publication Abstract from PubMed
The cation-permeable channel PKD2L1 forms a homomeric assembly as well as heteromeric associations with both PKD1 and PKD1L3, with the cytoplasmic regulatory domain (CRD) of PKD2L1 often playing a role in assembly and/or function. Our previous work indicated that the isolated PKD2L1 CRD assembles as a trimer in a manner dependent on the presence of a proposed oligomerization domain. Herein we describe the 2.7A crystal structure of a segment containing the PKD2L1 oligomerization domain which indicates that trimerization is driven by the beta-branched residues at the first and fourth positions of a heptad repeat (commonly referred to as "a" and "d") and by a conserved R-h-x-x-h-E salt bridge motif that is largely unique to parallel trimeric coiled coils. Further analysis of the PKD2L1 CRD indicates that trimeric association is sufficiently strong that no other species are present in solution in an analytical ultracentrifugation experiment at the lowest measurable concentration of 750nM. Conversely, mutation of the "a" and "d" residues leads to formation of an exclusively monomeric species, independent of concentration. Although both monomeric and WT CRDs are stable in solution and bind calcium with 0.9muM affinity, circular dichroism studies reveal that the monomer loses 25% more alpha-helical content than WT when stripped of this ligand, suggesting that the CRD structure is stabilized by trimerization in the ligand-free state. This stability could play a role in the function of the full-length complex, indicating that trimerization may be important for both homo- and possibly heteromeric assemblies of PKD2L1.
Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1.,Molland KL, Paul LN, Yernool DA Biochim Biophys Acta. 2011 Dec 13. PMID:22193359[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen XZ, Vassilev PM, Basora N, Peng JB, Nomura H, Segal Y, Brown EM, Reeders ST, Hediger MA, Zhou J. Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. Nature. 1999 Sep 23;401(6751):383-6. PMID:10517637 doi:http://dx.doi.org/10.1038/43907
- ↑ Huque T, Cowart BJ, Dankulich-Nagrudny L, Pribitkin EA, Bayley DL, Spielman AI, Feldman RS, Mackler SA, Brand JG. Sour ageusia in two individuals implicates ion channels of the ASIC and PKD families in human sour taste perception at the anterior tongue. PLoS One. 2009 Oct 8;4(10):e7347. doi: 10.1371/journal.pone.0007347. PMID:19812697 doi:http://dx.doi.org/10.1371/journal.pone.0007347
- ↑ Yu Y, Ulbrich MH, Li MH, Dobbins S, Zhang WK, Tong L, Isacoff EY, Yang J. Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex. Nat Commun. 2012 Dec 4;3:1252. doi: 10.1038/ncomms2257. PMID:23212381 doi:http://dx.doi.org/10.1038/ncomms2257
- ↑ DeCaen PG, Delling M, Vien TN, Clapham DE. Direct recording and molecular identification of the calcium channel of primary cilia. Nature. 2013 Dec 12;504(7479):315-8. doi: 10.1038/nature12832. PMID:24336289 doi:http://dx.doi.org/10.1038/nature12832
- ↑ Molland KL, Paul LN, Yernool DA. Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1. Biochim Biophys Acta. 2011 Dec 13. PMID:22193359 doi:10.1016/j.bbapap.2011.12.002
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