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==Mechanism of Transport==
==Mechanism of Transport==


YiiP's ability to export Zn<sup>2+</sup> from the cytoplasm is best described as an alternating access mechanism with Zn<sup>2+</sup>/H<sup>+</sup> antiport. YiiP has 2 major structural conformations which is supported by the crystallized structures 3H90 and 3J1Z (a YiiP homolog derived from Shewanella oneidensis). 3H90 shows YiiP in its outward-facing conformation and 3J1Z shows the YiiP homolog in an inward-facing conformation.
YiiP's ability to export Zn<sup>2+</sup> from the cytoplasm is best described as an alternating access mechanism with Zn<sup>2+</sup>/H<sup>+</sup> antiport. YiiP has 2 major structural conformations as shown by the crystallized structures 3H90 and 3J1Z (a YiiP homolog derived from Shewanella oneidensis). 3H90 shows YiiP in its outward-facing conformation and 3J1Z shows the YiiP homolog in an inward-facing conformation.
When YiiP is saturated with Zn<sup>2+</sup> it seems to favor the perplasmic/outward-facing conformation whereas when active sites are either empty or bound to H<sup>+</sup> the inward facing conformation is favored. This drives the export of Zn<sup>2+</sup> from the cytoplasm and enhances the coupling of the proton-motive force. Although YiiP exists as a homodimer both monomers can undergo conformation change independent of one other to produce the alternating access mechanism.
When YiiP is saturated with Zn<sup>2+</sup> it seems to favor the perplasmic/outward-facing conformation whereas when active sites are either empty or bound to H<sup>+</sup> the inward facing conformation is favored. This drives the export of Zn<sup>2+</sup> from the cytoplasm and enhances the coupling of the proton-motive force. Although YiiP exists as a homodimer both monomers can undergo conformation change independent of one other to produce the alternating access mechanism.


===Zn Induced Conformation Change===
===Zn Induced Conformation Change===


Conformation changes occur in the TMD and CTD, both of which are heavily influenced by the presence of Zn<sup>2+</sup>.Both of these conformation changes  
Conformation changes occur in the TMD and CTD, both of which are heavily influenced by the presence of Zn<sup>2+</sup>. Both of these conformation changes are focused around the charge interlocking mechanism that holds the dimer together. This is because a flexible loop that likes the CTD and the TMD which acts as a hinge for 
The conformation change directly involved with Zn<sup>2+</sup>/H<sup>+</sup> antiport occurs in the TMD as helix pivoting controls what environment site A is available to. Conformation change occurs when the transmembrane helix pairs TM3-TM6 pivot around cation binding site. It is believed that the energy for TMD conformation change comes from energy of binding each substrate. Changing to the outward from the inward-facing conformation causes a shift in TM5 which disrupts the tetrahedral geometry of active site A. This in turn decreases binding affinity site A has for Zn<sup>2+</sup> and causes Zn<sup>2+</sup> to leave which then favors change back to inward-facing conformation.
The conformation change directly involved with Zn<sup>2+</sup>/H<sup>+</sup> antiport occurs in the TMD as helix pivoting controls what environment site A is available to. Conformation change occurs when the transmembrane helix pairs TM3-TM6 pivot around cation binding site. It is believed that the energy for TMD conformation change comes from energy of binding each substrate. Changing to the outward from the inward-facing conformation causes a shift in TM5 which disrupts the tetrahedral geometry of active site A. This in turn decreases binding affinity site A has for Zn<sup>2+</sup> and causes Zn<sup>2+</sup> to leave site A which then favors change back to inward-facing conformation.
In contrast the main purpose of conformation change in the CTD is to stabilize the YiiP dimer and act a Zn<sup>2+</sup> sensor. Using FRET to measure the distance between the CTD of each monomer showed fluorescence quenching as the concentration Zn<sup>2+</sup> increased. It is not probable that Zn<sup>2+</sup> bound at site C works it way up to sites A or B, as C binds Zn<sup>2+</sup> with a much greater affinity.
In contrast the main purpose of conformation change in the CTD is to stabilize the YiiP dimer and acts as a Zn<sup>2+</sup> sensor. This is possible because of the flexible loop that links the TMD and the CTD. This loop harbors the charge interlock which serves as a hinge that allows movement of the CTD. Using FRET to measure the distance between the CTD of each monomer fluorescence quenching was observed as the concentration Zn<sup>2+</sup> increased, which supports that idea that Zn<sup>2+</sup> induces a stabilizing conformation change in the CTD.


===Allosteric Inhibition===
Zn binding to Active Site C causes a conformation change that reduces the affinity for Zn at Active Site A.
== Structural highlights ==


This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Stephanie Shoults, Joseph Thomas, Robin C. Gagnon, Geoffrey C. Hoops, Kyle Colston