Sandbox Reserved 1613: Difference between revisions
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Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two cavities seperated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the cytoplasm and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates. Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2. Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. | Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two cavities seperated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the cytoplasm and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates. Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2. Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. | ||
One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a hydrophobic membrane entrance lined by residues A397, V401, L539 | One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a hydrophobic membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both monomers. | ||
Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the motifs were on opposite sides of the protein. | Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the motifs were on opposite sides of the protein. | ||
<ref name=”Jackson”>PMID:29610494</ref> | <ref name=”Jackson”>PMID:29610494</ref> | ||
