View : 23 Download: 0
Homo- or hetero-dimerization of muscarinic receptor subtypes is not mediated by direct protein-protein interaction through intracellular and extracellular regions
- Homo- or hetero-dimerization of muscarinic receptor subtypes is not mediated by direct protein-protein interaction through intracellular and extracellular regions
- Kang Y.-K.; Yoon T.; Lee K.; Kim H.-J.
- Ewha Authors
- 김화정; 이경림; 윤태숙
- SCOPUS Author ID
- 김화정; 이경림
- Issue Date
- Journal Title
- Archives of Pharmacal Research
- vol. 26, no. 10, pp. 846 - 854
- SCIE; SCOPUS; KCI
- The oligomerization of G-proteincoupled receptors (GPCRs) has been shown to occur by various mechanisms, such as via disulfide covalent linkages, noncovalent (ionic, hydrophobic) interactions of the N-terminal, and/or transmembrane and/or intracellular domains. Interactions between GPCRs could involve an association between identical proteins (homomers) or non-identical proteins (heteromers), or between two monomers (to form dimers) or multiple monomers (to form oligomers). It is believed that muscarinic receptors may also be arranged into dimeric or oigomeric complexes, but no systematic experimental evidence exists concerning the direct physical interaction between receptor proteins as its mechanism. We undertook this study to determine whether muscarinic receptors form homomers or a heteromers by direct protein-protein interaction within the same or within different subtypes using a yeast two-hybrid system. Intracellular loops (i1, i2 and i3) and the C-terminal cytoplasmic tails (C) of human muscarinic (Hm) receptor subtypes, Hm1, Hm2 and Hm3, were cloned into the vectors (pB42AD and pLexA) of a two-hybrid system and examined for heteromeric or homodimeric interactions between the cytoplasmic domains. No physical interaction was observed between the intracellular domains of any of the Hm/Hm receptor sets tested. The results of our study suggest that the Hm1, Hm2 and Hm3 receptors do not form dimers or oligomers by interacting directly through either the hydrophilic intracellular domains or the C-terminal tail domains. To further investigate extracellular domain interactions, the N-terminus (N) and extracellular loops (o1 and o2) were also cloned into the two-hybrid vectors. Interactions of Hm2N with Hm2N, Hm2o1, Hm2o2, Hm3N, Hm3o1 or Hm3o2 were examined. The N-terminal domain of Hm2 was found to have no direct interaction with any extracellular domain. From our results, we excluded the possibility of a direct interaction between the muscarinic receptor subtypes (Hm1, Hm2 and Hm3) as a mechanism for homo- or hetero-meric dimerization/ oligomerization. On the other hand, it remains a possibility that interaction may occur indirectly or require proper conformation or subunit formation or hydrophobic region involvement.
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.