Sandbox 111: Difference between revisions
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'''Overall Structure''' | '''Overall Structure''' | ||
The M2 proton channel , made up of 97 residues, is a homotetramer transmembrane protein made up of 4 helices. The amino terminus of the protein is exposed to the outside environment, while the carboxy terminus is exposed to the internal environment. At pH 7.5, residues 18-23 form the N-terminus. Residues 25-46 create a transmembrane helix which forms a channel. Furthermore, residues 47-50 create a ‘short flexible loop,’ and residues 51-59 form a C-terminal amphipathic helix (Schnell). | |||
The loop created by residues 47-50 at the C-terminus connects the amphipathic helices to the transmembrane domain. The amphipathic helices lie perpendicular to the transmembrane helices. These amphipathic helices form a base that is resistant to changes in pH and therefore acts to stabilize the protein. It should be noted that the transmembrane helices are left handed while the amphipathic helices forming the base are right handed. These amphipathic helicves are also arranged head to tail (Schnell). | |||
The pore created by the four tansmembrane helices is constricted at the N-terminus by the methyl groups on Val 27. On the other end of the pore, interactions between Trp41 also create a blockage. The four helices are packed so tightly that van der Waals forces are created between the indole rings of Trp41. This forms a gate. Together, the interactions between Trp41 and Val27 block the passage of water through the pore. Furthermore, hydrogen bonds between Asp44 and Trp41 stabilize the gate. When the pH is lowered, the imidazole rings of His37 are protonated and the helices undergo electrostatic repulsion. This in turn breaks the Asp44 and Trp41 interactions and the gate will open. As previously mentioned, the base created by the amphipathic helices prevents the protein from dissociating. However, cysteins at the N-terminus create disulphide bonds that also act to prevent dissociation (Schnell). | |||
'''Drug Binding Site''' | '''Drug Binding Site''' | ||