Nat Genet. 1997 Jun;16(2):179-83.
PKD1 interacts with PKD2 through a probable coiled-coil domain.
Qian, F., Germino, F. J., Cai, Y., Zhang, X., Somlo, S., Germino, G. G.,
["Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA."]
["Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA."]
Autosomal dominant polycystic kidney disease (ADPKD) describes a group of at least three genetically distinct disorders with almost identical clinical features that collectively affects 1:1,000 of the population. Affected individuals typically develop large cystic kidneys and approximately one half develop end-stage renal disease by their seventh decade. It has been suggested that the diseases result from defects in interactive factors involved in a common pathway. The recent discovery of the genes for the two most common forms of ADPKD has provided an opportunity to test this hypothesis. We describe a previously unrecognized coiled-coil domain within the C terminus of the PKD1 gene product, polycystin, and demonstrate that it binds specifically to the C terminus of PKD2. Homotypic interactions involving the C terminus of each are also demonstrated. We show that naturally occurring pathogenic mutations of PKD1 and PKD2 disrupt their associations. We have characterized the structural basis of their heterotypic interactions by deletional and site-specific mutagenesis. Our data suggest that PKD1 and PKD2 associate physically in vivo and may be partners of a common signalling cascade involved in tubular morphogenesis.
PMID: 9171830
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Screening
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| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPP1 |
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PKD1/Polycystin-1 | Inference | Prediction | 9171830 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Validation: In vitro validation
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| Assay with recombinant proteins | Reference | |||||||||
| TRP channel construct | Interactor construct | |||||||||
| TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
| TRPP1 |
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PKD1/Polycystin-1 | Yeast two-hybrid | Human | 687-968 | Yeast | Human | 4088-4302 | Yeast | 9171830 |
(:
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
|
top
|
| Characterization
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|---|---|---|---|---|---|---|---|---|---|---|
| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPP1 |
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PKD1/Polycystin-1 | Yeast two-hybrid | Human | 742-872 | Human | 4214-4248 | 9171830 | ||
| TRPP1 |
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PKD1/Polycystin-1 | Fusion protein-pull down assay | Human | 742-872 | Human | 4214-4248 | 9171830 | ||
(:
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)