This pdb file contains a mutant form of AQP2. Serine256 has been substituted by alanine. This enabled the scientists to show the carboxyl terminus more completely. However, no Cd+2 ions were trapped in the crystallization. Normally it is very difficult to crystallize these very "fluid" terminal ends of the AQP2 structure. These tails are critical in the movement to and from the apical membrane.
These are some of the important residues essential in trafficking the aquaporin2 structures to the apical membrane
Intracellular cAMP triggers phosphorylation at Ser256 (red) which flags trafficking to apical membrane
This orange colored region (residues(230-243)) is critical for bonding to lysosomal trafficking regulator interacting protein 5 which is involved in internalizing AQP2 once it is no longer needed in the apical membrane. The leucines,shown here on this region in spacefilled fashion (Leucines 230,234,240,247) are also important in the positioning of the carboxyl terminal.
These residues(Pro225 and Pro226)(shown in purple) are important in the flexibility of the carboxyl terminus necessary for trafficking. Mutation at 226 results in the newly formed protein being retained in the endoplasmic reticulum.
These residues(Ser82 and Arg85...residues shown in green, with important hydrogen bonds in lime green) hold n-terminus in place critical for trafficking
These are some of the important mutations found in AQP2
Key mutations (Asn68, Ala70, Pro185) in the NPA region and (Arg 187) the selectivity filter preventing the pore from functioning correctly
Pore Narrowing mutations shown in green(V71 and V168)
Critical Mutations interfering with Glycosylation (and other processes) (Thr125, Thr126, Ser148, Asp150) shown in red
Mutation here (Arg123 shown in purple) causes the structure to remain in the Golgi Apparatus
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AQP2 Tetramer
(based on 4NEF.pdb)
This model shows all four chains of the Aquaporin2 tetramer. Also represented are the important divalent bonding domains important in the trafficking of AQP2 to and from intracellular vesicles.
The important residues essential in trafficking the aquaporin2 tetramer structure to the apical membrane.
Illustrating just one monomer, the important residues essential in trafficking the aquaporin2 structure to the apical membrane.
This orange colored region (residues 230-234) is critial for bonding to lysomal trafficking regulator interacting protein 5 which is involved in internalizing AQP2 once it is no longer needed in the apical membrane. The leucines, shown here on the this region in spacefilled fashion (Leucines 230, 234, 240, 247) are also important in the positioning of the carboxyl terminal.
These residues(Pro225 and Pro226) (shown in purple) are important in the flexibility of the carboxyl terminus. necessary for trafficking
These residues(Glu3, Ser82 and Arg85...residues shown in green, with important hydrogen bonds in lime green) hold n-terminus in place critical for trafficking
These residues (blue) holding cadmium ions(pictured in pink)(in vitro)(in vivo, calcium is the critical cation) in place critical for trafficking.
These are some of the mutation locations shown on the tetramer structure.
These are some of the mutation locations shown on the monomer structure.
Key mutations shown in orange (Asn68, Ala70, Pro185)in the NPA region and selectivity filter region(Arg187) preventing the pore from functioning correctly.
Pore Narrowing mutations shown in green (Val71 and Val168)
Critical Mutations interfering with Glycosylation (and other processes) (Thr125, Thr126, Ser148, Asp150) shown in red
Mutations here (Arg123 shown in purple) causes the structure to remain in the Golgi Apparatus
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