Nat Commun. 2012;3:1252. doi: 10.1038/ncomms2257.
Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex.
Yu, Y., Ulbrich, M. H., Li, M. H., Dobbins, S., Zhang, W. K., Tong, L., Isacoff, E. Y., Yang, J.,
["Department of Biological Sciences, Columbia University, New York, New York 10027, USA."]
["Department of Biological Sciences, Columbia University, New York, New York 10027, USA."]
Polycystic kidney disease (PKD) family proteins associate with transient receptor potential (TRP) channel family proteins to form functionally important complexes. PKD proteins differ from known ion channel-forming proteins and are generally thought to act as membrane receptors. Here we find that PKD1L3, a PKD protein, functions as a channel-forming subunit in an acid-sensing heteromeric complex formed by PKD1L3 and TRPP3, a TRP channel protein. Single amino-acid mutations in the putative pore region of both proteins alter the channel's ion selectivity. The PKD1L3/TRPP3 complex in the plasma membrane of live cells contains one PKD1L3 and three TRPP3. A TRPP3 C-terminal coiled-coil domain forms a trimer in solution and in crystal, and has a crucial role in the assembly and surface expression of the PKD1L3/TRPP3 complex. These results demonstrate that PKD subunits constitute a new class of channel-forming proteins, enriching our understanding of the function of PKD proteins and PKD/TRPP complexes.
PMID: 23212381
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Validation: In vivo validation
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| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPP2 |
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PKD1L3/Polycystin-1L3 | Co-immunoprecipitation | Xenopus oocyte | Human | Full-length | Human | Full-length | 23212381 | |
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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| Characterization
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| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPP2 |
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PKD1L3/Polycystin-1L3 | Single-molecule photobleaching | 3:1 | 23212381 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Functional consequence
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| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPP2 |
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PKD1L3/Polycystin-1L3 | Patch clamp | New channel creation | 23212381 | |||||||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)