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===DNA-Binding Domain (DBD) (residues 555-623)===

DBD is a cysteine-rich region that is the most highly conserved one of the steroid hormone nuclear receptor family <ref name="Structure" />, but it has been shown that binding of selective androgen response elements (AREs) allow the specific activation functions of the AR. They facilitate direct DNA binding of the AR to the promoter and enhancer regions of AR-regulated genes, thereby allowing the activation functions of the N-terminal and ligand binding domains to stimulate or repress the transcription of these genes <ref name="Bench to Bedside" />.

AR is a dimer, like other steroid receptors, that binds to promoter DNA response elements consisting of two equal, common hexameric half-sites, separated by a 3 base-pair spacer <ref name="Structure" />'''IMAGEN DEL DÍMERO''', and this domain is critical for AR function, because it plays a role in dimerization and binding of dimerized AR to select motifs on target DNA <ref name="~~AR”~~ />.

AR is a dimer, like other steroid receptors, that binds to promoter DNA response elements consisting of two equal, common hexameric half-sites, separated by a 3 base-pair spacer <ref name="Structure" />'''IMAGEN DEL DÍMERO''', and this domain is critical for AR function, because it plays a role in dimerization and binding of dimerized AR to select motifs on target DNA <ref name="AR" />.

Each DBD monomer has a core composed of two zinc finger motifs, which consists of four cysteine residues that coordinate a zinc ion <ref name="Structure" />. The first is closer to the NTD which has the P box, which is identical in all the family, and controls the DNA binding specificity at AREs, located in the regulatory regions of genes <ref name="~~AR”~~ />.

Each DBD monomer has a core composed of two zinc finger motifs, which consists of four cysteine residues that coordinate a zinc ion <ref name="Structure" />. The first is closer to the NTD which has the P box, which is identical in all the family, and controls the DNA binding specificity at AREs, located in the regulatory regions of genes <ref name="AR" />.

The second zinc finger motif facilitates AR dimerization via the D box. Additionally, a nuclear localization signal (NLS) is localized at the junction between the DBD and the hinge region and it binds to importin-α and facilitates nuclear translocation <ref name="~~AR”~~ />. This is because passive transport across the nuclear pore complex has been suggested ranging from 20–40 kDa, in contrast, the AR, which is 110 kDa in size, requires help to be actively transported upon ligand binding <ref name="Structure" />.

The second zinc finger motif facilitates AR dimerization via the D box. Additionally, a nuclear localization signal (NLS) is localized at the junction between the DBD and the hinge region and it binds to importin-α and facilitates nuclear translocation <ref name="AR" />. This is because passive transport across the nuclear pore complex has been suggested ranging from 20–40 kDa, in contrast, the AR, which is 110 kDa in size, requires help to be actively transported upon ligand binding <ref name="Structure" />.

The DBD is linked to the ligand binding domain by a flexible hinge region (residues 623-665), which is a linker poorly conserved. Once in the nucleus, this region also interacts with the DBD to identify specific sequences for AR binding. It controls the AR activation and degradation. Consequently, mutations in the hinge region can lead to enhanced AR potency <ref name="~~AR”~~ />.

The DBD is linked to the ligand binding domain by a flexible hinge region (residues 623-665), which is a linker poorly conserved. Once in the nucleus, this region also interacts with the DBD to identify specific sequences for AR binding. It controls the AR activation and degradation. Consequently, mutations in the hinge region can lead to enhanced AR potency <ref name="AR" />.

===Ligand-Binding Domain (LBD) (residues 665-919)===

The LBD, located at the C-terminal, is the main target of AR inhibitors <ref name="~~AR”~~ />. It consists of eleven α-helixes in the ligand binding pocket, with reposition upon androgen binding, converting into the activation function 2 (AF-2) domain. Unlike other nuclear receptors, the AR does not have H2, which is instead replaced by a long flexible linker <ref name="Structure" />. The LBD binds motifs in the NTD and in AR-specific cofactors and coactivators. Moreover, LBD-LBD homodimerization of AR is essential in the proper functioning of the receptos <ref name="~~AR”~~ />.

The LBD, located at the C-terminal, is the main target of AR inhibitors <ref name="AR" />. It consists of eleven α-helixes in the ligand binding pocket, with reposition upon androgen binding, converting into the activation function 2 (AF-2) domain. Unlike other nuclear receptors, the AR does not have H2, which is instead replaced by a long flexible linker <ref name="Structure" />. The LBD binds motifs in the NTD and in AR-specific cofactors and coactivators. Moreover, LBD-LBD homodimerization of AR is essential in the proper functioning of the receptos <ref name="AR" />.

This domain has been structurally well characterized by crystallography and a number of mutations have been identified. It is important because not all mutations affect ligand binding, but some of them may disrupt androgen induced interaction of the N-terminal motif and C-terminal AF-2 <ref name="~~AR”~~ />.

This domain has been structurally well characterized by crystallography and a number of mutations have been identified. It is important because not all mutations affect ligand binding, but some of them may disrupt androgen induced interaction of the N-terminal motif and C-terminal AF-2 <ref name="AR" />.

==Transcriptional Activation Function==

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@@ Line 10: / Line 10: @@
 ===DNA-Binding Domain (DBD) (residues 555-623)===
 DBD is a cysteine-rich region that is the most highly conserved one of the steroid hormone nuclear receptor family <ref name="Structure" />, but it has been shown that binding of selective androgen response elements (AREs) allow the specific activation functions of the AR. They facilitate direct DNA binding of the AR to the promoter and enhancer regions of AR-regulated genes, thereby allowing the activation functions of the N-terminal and ligand binding domains to stimulate or repress the transcription of these genes <ref name="Bench to Bedside" />.
-AR is a dimer, like other steroid receptors, that binds to promoter DNA response elements consisting of two equal, common hexameric half-sites, separated by a 3 base-pair spacer <ref name="Structure" />'''IMAGEN DEL DÍMERO''', and this domain is critical for AR function, because it plays a role in dimerization and binding of dimerized AR to select motifs on target DNA <ref name="AR” />.
+AR is a dimer, like other steroid receptors, that binds to promoter DNA response elements consisting of two equal, common hexameric half-sites, separated by a 3 base-pair spacer <ref name="Structure" />'''IMAGEN DEL DÍMERO''', and this domain is critical for AR function, because it plays a role in dimerization and binding of dimerized AR to select motifs on target DNA <ref name="AR" />.
-Each DBD monomer has a core composed of two zinc finger motifs, which consists of four cysteine residues that coordinate a zinc ion <ref name="Structure" />. The first is closer to the NTD which has the P box, which is identical in all the family, and controls the DNA binding specificity at AREs, located in the regulatory regions of genes <ref name="AR” />.
+Each DBD monomer has a core composed of two zinc finger motifs, which consists of four cysteine residues that coordinate a zinc ion <ref name="Structure" />. The first is closer to the NTD which has the P box, which is identical in all the family, and controls the DNA binding specificity at AREs, located in the regulatory regions of genes <ref name="AR" />.
-The second zinc finger motif facilitates AR dimerization via the D box. Additionally, a nuclear localization signal (NLS) is localized at the junction between the DBD and the hinge region and it binds to importin-α and facilitates nuclear translocation <ref name="AR” />. This is because passive transport across the nuclear pore complex has been suggested ranging from 20–40 kDa, in contrast, the AR, which is 110 kDa in size, requires help to be actively transported upon ligand binding <ref name="Structure" />.
+The second zinc finger motif facilitates AR dimerization via the D box. Additionally, a nuclear localization signal (NLS) is localized at the junction between the DBD and the hinge region and it binds to importin-α and facilitates nuclear translocation <ref name="AR" />. This is because passive transport across the nuclear pore complex has been suggested ranging from 20–40 kDa, in contrast, the AR, which is 110 kDa in size, requires help to be actively transported upon ligand binding <ref name="Structure" />.
-The DBD is linked to the ligand binding domain by a flexible hinge region (residues 623-665), which is a linker poorly conserved. Once in the nucleus, this region also interacts with the DBD to identify specific sequences for AR binding. It controls the AR activation and degradation. Consequently, mutations in the hinge region can lead to enhanced AR potency <ref name="AR” />.
+The DBD is linked to the ligand binding domain by a flexible hinge region (residues 623-665), which is a linker poorly conserved. Once in the nucleus, this region also interacts with the DBD to identify specific sequences for AR binding. It controls the AR activation and degradation. Consequently, mutations in the hinge region can lead to enhanced AR potency <ref name="AR" />.
 ===Ligand-Binding Domain (LBD) (residues 665-919)===
-The LBD, located at the C-terminal, is the main target of AR inhibitors <ref name="AR” />. It consists of eleven α-helixes in the ligand binding pocket, with reposition upon androgen binding, converting into the activation function 2 (AF-2) domain. Unlike other nuclear receptors, the AR does not have H2, which is instead replaced by a long flexible linker <ref name="Structure" />. The LBD binds motifs in the NTD and in AR-specific cofactors and coactivators. Moreover, LBD-LBD homodimerization of AR is essential in the proper functioning of the receptos <ref name="AR” />.
+The LBD, located at the C-terminal, is the main target of AR inhibitors <ref name="AR" />. It consists of eleven α-helixes in the ligand binding pocket, with reposition upon androgen binding, converting into the activation function 2 (AF-2) domain. Unlike other nuclear receptors, the AR does not have H2, which is instead replaced by a long flexible linker <ref name="Structure" />. The LBD binds motifs in the NTD and in AR-specific cofactors and coactivators. Moreover, LBD-LBD homodimerization of AR is essential in the proper functioning of the receptos <ref name="AR" />.
-This domain has been structurally well characterized by crystallography and a number of mutations have been identified. It is important because not all mutations affect ligand binding, but some of them may disrupt androgen induced interaction of the N-terminal motif and C-terminal AF-2 <ref name="AR” />.
+This domain has been structurally well characterized by crystallography and a number of mutations have been identified. It is important because not all mutations affect ligand binding, but some of them may disrupt androgen induced interaction of the N-terminal motif and C-terminal AF-2 <ref name="AR" />.
 ==Transcriptional Activation Function==