Linked Life Data

9687580

Source:http://linkedlifedata.com/resource/pubmed/id/9687580

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-8-31
pubmed:abstractText
To investigate the roles of individual transmembrane segments (TM) of the human D3 dopamine receptor in its ligand-receptor interactions, we generated chimeric receptors in which its TMs were replaced, one at a time, partially or entirely, by the corresponding TM of the homologous human D1 receptor. Ligand binding properties of the chimeras, as expressed heterologously in Sf9 cells using recombinant baculoviruses, indicate that the critical binding regions for D3-selective (over D1) ligands reside at narrow regions (6 to 8 residues) near the extracellular surface for TMI, II, IV and VI, while TMV seems to be minimally involved in the ligand selectivity. For TMIII and TMVII, the critical regions seem to be deeper, involving at least the 10 residues near the extracellular surface for TMIII, and the entire TM segment for TMVII. This is based on our current observations that the chimeras with the D3 sequence in the critical regions, although the rest of the TM is of D1 origin (except TMVII), showed the binding properties indistinguishable from those of the wild-type receptor. The chimeras with the D1 sequence in the regions, on the other hand, showed ligand binding characteristics wildly variable depending on substituted TMs: Most marked decreases in ligand affinities were observed with the chimeras of TMIII and VII, and intermediate changes with those of TMIV and VI. Replacements of TMV produced no appreciable effects on the affinities of 14 test ligands (except for one). The chimeras of TMI and II with the D1 sequence in the critical regions showed no appreciable specific binding for several radioactive D3-selective ligands, possibly reflecting their critical roles in assembly and folding of the receptor. These critical regions of the D3 receptor were highly homologous to those of the D2 receptor, except for several nonconservatively substituted residues, which could be exploited to develop ligands selective for the D3 over D2 dopamine receptor or vice versa.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
379-88
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Identification of transmembrane regions critical for ligand binding to the human D3 dopamine receptor using various D3/D1 transmembrane chimeras.
pubmed:affiliation
CNS Diseases Research, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001, USA.
pubmed:publicationType
Journal Article