Identification of amino acid residues that direct differential ligand selectivity of mammalian and nonmammalian V1a type receptors for arginine vasopressin and vasotocin: Insights into molecular coevolution of V1a type receptors and their ligands

Sujata Acharjee, Jean Luc Do-Rego, Da Young Oh, Ryun Sup Ahn, Han Choe, Hubert Vaudry, Kyungjin Kim, Jae Young Seong, Hyuk Bang Kwon

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Arginine vasotocin (VT) is the ortholog in all nonmammalian vertebrates of arginine vasopressin (AVP) in mammals. We have previously cloned an amphibian V1a-type vasotocin receptor (VT1R) that exhibited higher sensitivity for VT than AVP, while the mammalian V1a type receptor (V1aR) responded better to AVP than VT. In the present study, we identified the amino acid residues that confer differential ligand selectivity for AVP and VT between rat V1aR and bullfrog VT1R (bfVT1R). A chimeric rat V1aR having transmembrane domain (TMD) VI to the carboxyl-terminal tail (C-tail) of bfVT1R showed a reverse ligand preference for AVP and VT, whereas a chimeric VT1R with TMD VI to the C-tail of rat V1aR showed a great increase in sensitivity for AVP. A single mutation (Ile 315(6.53) to Thr) in TMD VI of V1aR increased the sensitivity for VT, while a single mutation (Phe313(6.51) to Tyr or Pro 334(7.33) to Thr) reduced sensitivity toward AVP. Interestingly the triple mutation (Phe313(6.51) to Tyr, Ile6.53 to Thr, and Pro7.33 to Thr) of V1aR increased sensitivity to VT but greatly reduced sensitivity to AVP, behaving like bfVT1R. Further, like V1aR, a double mutant (Tyr306(6.51) to Phe and Thr327(7.33) to Pro) of bfVT1R showed an increased sensitivity to AVP. These results suggest that Phe/Tyr6.51, Ile/Thr6.53, and Pro/Thr7.33 are responsible for the differential ligand selectivity between rat V1aR and bfVT1R. This information regarding the molecular interaction of VT/AVP with their receptors may have important implications for the development of novel AVP analogs.

Original languageEnglish
Pages (from-to)54445-54453
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number52
DOIs
Publication statusPublished - 2004 Dec 24
Externally publishedYes

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Vasopressin Receptors
Arginine Vasopressin
Vasotocin
Ligands
Amino Acids
Rana catesbeiana
Rats
Mutation
Tail
vasotocin receptor
Mammals
Molecular interactions
Amphibians
Vertebrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of amino acid residues that direct differential ligand selectivity of mammalian and nonmammalian V1a type receptors for arginine vasopressin and vasotocin : Insights into molecular coevolution of V1a type receptors and their ligands. / Acharjee, Sujata; Do-Rego, Jean Luc; Oh, Da Young; Ahn, Ryun Sup; Choe, Han; Vaudry, Hubert; Kim, Kyungjin; Seong, Jae Young; Kwon, Hyuk Bang.

In: Journal of Biological Chemistry, Vol. 279, No. 52, 24.12.2004, p. 54445-54453.

Research output: Contribution to journalArticle

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abstract = "Arginine vasotocin (VT) is the ortholog in all nonmammalian vertebrates of arginine vasopressin (AVP) in mammals. We have previously cloned an amphibian V1a-type vasotocin receptor (VT1R) that exhibited higher sensitivity for VT than AVP, while the mammalian V1a type receptor (V1aR) responded better to AVP than VT. In the present study, we identified the amino acid residues that confer differential ligand selectivity for AVP and VT between rat V1aR and bullfrog VT1R (bfVT1R). A chimeric rat V1aR having transmembrane domain (TMD) VI to the carboxyl-terminal tail (C-tail) of bfVT1R showed a reverse ligand preference for AVP and VT, whereas a chimeric VT1R with TMD VI to the C-tail of rat V1aR showed a great increase in sensitivity for AVP. A single mutation (Ile 315(6.53) to Thr) in TMD VI of V1aR increased the sensitivity for VT, while a single mutation (Phe313(6.51) to Tyr or Pro 334(7.33) to Thr) reduced sensitivity toward AVP. Interestingly the triple mutation (Phe313(6.51) to Tyr, Ile6.53 to Thr, and Pro7.33 to Thr) of V1aR increased sensitivity to VT but greatly reduced sensitivity to AVP, behaving like bfVT1R. Further, like V1aR, a double mutant (Tyr306(6.51) to Phe and Thr327(7.33) to Pro) of bfVT1R showed an increased sensitivity to AVP. These results suggest that Phe/Tyr6.51, Ile/Thr6.53, and Pro/Thr7.33 are responsible for the differential ligand selectivity between rat V1aR and bfVT1R. This information regarding the molecular interaction of VT/AVP with their receptors may have important implications for the development of novel AVP analogs.",
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T1 - Identification of amino acid residues that direct differential ligand selectivity of mammalian and nonmammalian V1a type receptors for arginine vasopressin and vasotocin

T2 - Insights into molecular coevolution of V1a type receptors and their ligands

AU - Acharjee, Sujata

AU - Do-Rego, Jean Luc

AU - Oh, Da Young

AU - Ahn, Ryun Sup

AU - Choe, Han

AU - Vaudry, Hubert

AU - Kim, Kyungjin

AU - Seong, Jae Young

AU - Kwon, Hyuk Bang

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