Proton control of amino acid transport and protein trafficking
<p>Protons play a key role in various biological process ranging from substrate binding, protein conformational change, oligomerisation processes as well as altering the chemical environment within the protein. Computational techniques such as molecular dynamics or quantum mechanics calculatio...
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| Médium: | Diplomová práce |
| Jazyk: | English |
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2020
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| Shrnutí: | <p>Protons play a key role in various biological process ranging from substrate binding, protein conformational change, oligomerisation processes as well as altering the chemical environment within the protein. Computational techniques such as molecular dynamics
or quantum mechanics calculations are excellent tools at tracking the proton as well as examining its effect on the protein.</p>
<p>Secondary active transporters such as the SLC36 superfamily use the proton gradient to drive the transport of an amino acids against its concentration gradient. This thesis shows that the deprotonation of a key glutamate destabilises the inward-occluded state, which leads to the conformational change to the inward-open state. The conformational change clears the steric barrier from the intracellular gate to allow the egress of the substrate.</p>
<p>The KDEL receptor binds ER resident proteins in the Golgi and returns them to the ER. The binding of the ER retention tag (KDEL) occurs in a pH dependent fashion. This thesis shows that the protonation of a key histidine (H12) facilitates the formation of a low- barrier hydrogen bond, which locks the KDEL tag in the receptor, where as the deprotonation of this histidine weakens the hydrogen bond which allows the release of the KDEL tag.</p>
<p>The trafficking of the KDEL receptor between the ER and Golgi has been shown to involve oligomerisation. This thesis shows that the KDEL-bound KDEL receptor and the apo receptor could form dimers with different interfaces. The apo receptor could potentially form a nonamer when another key histidine (H150) is deprotonated.
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