Two highly conserved glutamate residues critical for type III sodium-dependent phosphate transport revealed by uncoupling transport function from retroviral receptor function.

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Citation

Bottger P, Pedersen L

Two highly conserved glutamate residues critical for type III sodium-dependent phosphate transport revealed by uncoupling transport function from retroviral receptor function.

J Biol Chem. 2002 Nov 8;277(45):42741-7. Epub 2002 Aug 29.

PubMed ID
12205090 [ View in PubMed
]
Abstract

Type III sodium-dependent phosphate (NaP(i)) cotransporters, Pit1 and Pit2, have been assigned housekeeping P(i) transport functions and suggested involved in chondroblastic and osteoblastic mineralization and ectopic calcification. Both proteins exhibit dual function, thus, besides being transporters, they also serve as receptors for several gammaretroviruses. We here show that it is possible to uncouple transport and receptor functions of a type III NaP(i) cotransporter and thus exploit the retroviral receptor function as a control for proper processing and folding of mutant proteins. Thus exchanging two putative transmembranic glutamate residues in human Pit2, Glu(55) and Glu(575), with glutamine or with lysine severely impaired or knocked out, respectively, P(i) transport function, but left viral receptor function undisturbed. Both glutamates are conserved in type III NaP(i) cotransporters, in fungal NaP(i) cotransporters PHO-4 and Pho89, and in other known or putative phosphate permeases from a number of species and are the first residues shown to be critical for type III NaP(i) cotransport. Their putative transmembranic positions together with the presented data are consistent with Glu(55) and Glu(575) being parts of a cation liganding site or playing roles in conformational changes associated with substrate transport. Finally, the results also show that Pit2 retroviral receptor function per se is not dependent on Pit2 P(i) transport function.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Sodium-dependent phosphate transporter 2Q08357Details