{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

BME417HW5 - BME 417 HW5 Transporter or Paddle A Debate on...

Info icon This preview shows pages 1–3. Sign up to view the full content.

View Full Document Right Arrow Icon
1 BME 417 HW5 Transporter or Paddle: A Debate on Voltage Sensor Models With the elucidation of the voltage-sensitive KvAP channel structure by MacKinnon’s group, we would expect the voltage sensing model debate to come to a conclusive end. But instead, it introduced a controversial new model that fueled a barrage of debates. Is it transporter or paddle? Both models have strong supporting evidences, and, as a corollary, strong counter evidences. This discussion aims to summarize the evidences for both models, and decide where I would place my money. It all started with a publication by the MacKinnon’s group in 2003, X-ray structure of a voltage-dependent K+ channel and it’s accompanying paper, The principle of gating charge movement in a voltage-dependent K+ channel . In the first paper, a structure of a voltage-dependent K+ channel is presented. To the surprise of everyone, the voltage- sensitive S4 segment is found in an odd position – near the cytoplasmic surface of the membrane. This finding is at odd with previous studies showing that the S4 segment is accessible from the extracellular surface. One possible explanation is that this may not be a natural conformation of the channel, and it is an artifact of the crystallization process. In a subsequent experiment, they produced and isolated only the S1-S4 segment of the channel, and established that the segment is in its natural conformation through a toxin-binding test. Using this shorter segment, they showed that the S4 segment is capable of adopting this new found position naturally. These findings led them to propose a new model for the gating movement of the S4 segment. In the new model, the S4 segment forms a voltage sensitive paddle at the periphery of the channel. The 4 Arg residues responsible for the gating current are located at the moving end of the paddle. The pivoted end is attached to the rest of the channel, close to the
Image of page 1

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
2 cytoplasmic surface. In the close conformation, the Arg residues are in the lipid bilayer near to the cytoplasmic surface. Upon depolarization of the membrane, the S4 paddle swings through the lipid bilayer, bringing the charged Arg residues to the extracellular surface. Some key features that this model entails are: (1) movement of charges across large distances and (2) charged residues reside within the lipid bilayer. This new model is
Image of page 2
Image of page 3
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern