Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids
The mineralocorticoid receptor (MR) is primarily localized in the cytoplasm of the cell in the absence of ligand. The first step in the genomic-dependent mechanism of action of mineralocorticoids is the binding of steroid to the MR, which in turn triggers MR nuclear translocation. The regulation of...
Guardado en:
| Autor principal: | |
|---|---|
| Publicado: |
2004
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v217_n1-2_p167_Galigniana http://hdl.handle.net/20.500.12110/paper_03037207_v217_n1-2_p167_Galigniana |
| Aporte de: |
| id |
paper:paper_03037207_v217_n1-2_p167_Galigniana |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_03037207_v217_n1-2_p167_Galigniana2023-06-08T15:29:02Z Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids Burton, Gerardo 11,19-Oxidoprogesterone Aldosterone Dynein Immunophilins Natriuresis Trafficking 11,19 oxidoprogesterone 11beta hydroxyprogesterone 5alpha pregnane 3,20 dione 5beta dihydroprogesterone 6,19 oxidoprogesterone aldosterone deoxycorticosterone dynein adenosine triphosphatase ligand mineralocorticoid mineralocorticoid receptor pregn 4 ene 3,11,20 trione pregnane derivative progesterone derivative steroid unclassified drug binding affinity cell nucleus complex formation conference paper conformation cytoplasm dose response drug effect drug half life drug structure in vivo study ligand binding molecular dynamics molecular interaction nonhuman priority journal protein function structure activity relation Active Transport, Cell Nucleus Animals Cell Nucleus Cytoplasm Gene Expression Regulation Humans Pregnenediones Protein Binding Protein Conformation Rats Receptors, Mineralocorticoid Signal Transduction Structure-Activity Relationship Transcription Factors The mineralocorticoid receptor (MR) is primarily localized in the cytoplasm of the cell in the absence of ligand. The first step in the genomic-dependent mechanism of action of mineralocorticoids is the binding of steroid to the MR, which in turn triggers MR nuclear translocation. The regulation of hormone-binding to MR is complex and involves a multifactorial mechanism, making it difficult to determine the optimal structure of a steroid for activating the MR and promoting its nuclear translocation. Here we review the structure-activity relationship for several pregnanesteroids that possess various functional groups, and suggest that a flat conformation of the ligand rather than the presence of particular chemical groups is a critical parameter for the final biological effect in vivo. We also discuss how the MR undergoes differential conformational changes according to the nature of the bound ligand, which in turn affects the dynein-dependent retrograde rate of movement for the steroid/receptor complex. © 2003 Elsevier Ireland Ltd. All rights reserved. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v217_n1-2_p167_Galigniana http://hdl.handle.net/20.500.12110/paper_03037207_v217_n1-2_p167_Galigniana |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
11,19-Oxidoprogesterone Aldosterone Dynein Immunophilins Natriuresis Trafficking 11,19 oxidoprogesterone 11beta hydroxyprogesterone 5alpha pregnane 3,20 dione 5beta dihydroprogesterone 6,19 oxidoprogesterone aldosterone deoxycorticosterone dynein adenosine triphosphatase ligand mineralocorticoid mineralocorticoid receptor pregn 4 ene 3,11,20 trione pregnane derivative progesterone derivative steroid unclassified drug binding affinity cell nucleus complex formation conference paper conformation cytoplasm dose response drug effect drug half life drug structure in vivo study ligand binding molecular dynamics molecular interaction nonhuman priority journal protein function structure activity relation Active Transport, Cell Nucleus Animals Cell Nucleus Cytoplasm Gene Expression Regulation Humans Pregnenediones Protein Binding Protein Conformation Rats Receptors, Mineralocorticoid Signal Transduction Structure-Activity Relationship Transcription Factors |
| spellingShingle |
11,19-Oxidoprogesterone Aldosterone Dynein Immunophilins Natriuresis Trafficking 11,19 oxidoprogesterone 11beta hydroxyprogesterone 5alpha pregnane 3,20 dione 5beta dihydroprogesterone 6,19 oxidoprogesterone aldosterone deoxycorticosterone dynein adenosine triphosphatase ligand mineralocorticoid mineralocorticoid receptor pregn 4 ene 3,11,20 trione pregnane derivative progesterone derivative steroid unclassified drug binding affinity cell nucleus complex formation conference paper conformation cytoplasm dose response drug effect drug half life drug structure in vivo study ligand binding molecular dynamics molecular interaction nonhuman priority journal protein function structure activity relation Active Transport, Cell Nucleus Animals Cell Nucleus Cytoplasm Gene Expression Regulation Humans Pregnenediones Protein Binding Protein Conformation Rats Receptors, Mineralocorticoid Signal Transduction Structure-Activity Relationship Transcription Factors Burton, Gerardo Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids |
| topic_facet |
11,19-Oxidoprogesterone Aldosterone Dynein Immunophilins Natriuresis Trafficking 11,19 oxidoprogesterone 11beta hydroxyprogesterone 5alpha pregnane 3,20 dione 5beta dihydroprogesterone 6,19 oxidoprogesterone aldosterone deoxycorticosterone dynein adenosine triphosphatase ligand mineralocorticoid mineralocorticoid receptor pregn 4 ene 3,11,20 trione pregnane derivative progesterone derivative steroid unclassified drug binding affinity cell nucleus complex formation conference paper conformation cytoplasm dose response drug effect drug half life drug structure in vivo study ligand binding molecular dynamics molecular interaction nonhuman priority journal protein function structure activity relation Active Transport, Cell Nucleus Animals Cell Nucleus Cytoplasm Gene Expression Regulation Humans Pregnenediones Protein Binding Protein Conformation Rats Receptors, Mineralocorticoid Signal Transduction Structure-Activity Relationship Transcription Factors |
| description |
The mineralocorticoid receptor (MR) is primarily localized in the cytoplasm of the cell in the absence of ligand. The first step in the genomic-dependent mechanism of action of mineralocorticoids is the binding of steroid to the MR, which in turn triggers MR nuclear translocation. The regulation of hormone-binding to MR is complex and involves a multifactorial mechanism, making it difficult to determine the optimal structure of a steroid for activating the MR and promoting its nuclear translocation. Here we review the structure-activity relationship for several pregnanesteroids that possess various functional groups, and suggest that a flat conformation of the ligand rather than the presence of particular chemical groups is a critical parameter for the final biological effect in vivo. We also discuss how the MR undergoes differential conformational changes according to the nature of the bound ligand, which in turn affects the dynein-dependent retrograde rate of movement for the steroid/receptor complex. © 2003 Elsevier Ireland Ltd. All rights reserved. |
| author |
Burton, Gerardo |
| author_facet |
Burton, Gerardo |
| author_sort |
Burton, Gerardo |
| title |
Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids |
| title_short |
Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids |
| title_full |
Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids |
| title_fullStr |
Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids |
| title_full_unstemmed |
Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids |
| title_sort |
molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids |
| publishDate |
2004 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v217_n1-2_p167_Galigniana http://hdl.handle.net/20.500.12110/paper_03037207_v217_n1-2_p167_Galigniana |
| work_keys_str_mv |
AT burtongerardo molecularmechanismofactivationandnucleartranslocationofthemineralocorticoidreceptoruponbindingofpregnanesteroids |
| _version_ |
1768546492661891072 |