SignalingLectureFinal

Cooperativity and binding interestingly many if not

Info icon This preview shows pages 15–22. Sign up to view the full content.

View Full Document Right Arrow Icon
Cooperativity and binding Interestingly, many (if not most) of the real world binding problems we care about in biology do not satisfy the simple binding model (sometimes called the Langmuir adsorption isotherm) we have worked out so far. The classic example (i.e. the hydrogen atom of binding problems) is hemoglobin.
Image of page 15

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

View Full Document Right Arrow Icon
Hemoglobin as a case study in cooperativity several 100s hemoglobin molecules Oxygen binds to heme on the hemoglobin molecules Hemoglobin - the classic example of ligand-receptor binding Cooperativity: the binding energy for a given ligand depends upon the # of ligands that are already bound to the receptor Intuitively: conformational change upon binding => the next ligand experiences a different binding energy apps.uwhealth.org The heme group includes a porphyrin ring (gray line) + iron The protein hemoglobin: 4 polypeptide chains (2 α -chains, 2 β - chains), each carries a heme group => protein can bind up to 4 molecules of O 2
Image of page 16
The nature of the Hill function
Image of page 17

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

View Full Document Right Arrow Icon
Hemoglobin as a case study in cooperativity Hemoglobin-oxygen binding: language of two-states occupation variables. State of system is described with the vector where σ i : σ i = 0 (unbound), σ i = 1 (bound) Q.: what is the average # of bound O 2 molecules as a function of the O 2 concentration (or partial pressure)? A toy model of a dimoglobin To illustrate the idea of cooperativity: imagine a fictitious dimoglobin [=dimeric hemoglobin] molecule which has 2 O 2 binding sites ( e.g., clams ) => 4 distinct states The energy of the system: Energy associated with O 2 being bound to one of the 2 sites measure of the cooperativity
Image of page 18
A toy model of a dimoglobin The grand partition function (sum over the 4 states): => compute the probabilities for each classes of states: unoccupied, single occupancy, double occupancy Single occupancy Both sites occupied Parameters used: Δε =–5 k B T, J= –2.5 k B T, c 0 = 760 mmHg
Image of page 19

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

View Full Document Right Arrow Icon
Talking across the membrane Membrane proteins are characterized in some cases by transmembrane alpha helices and cytosolic domain that passes along the signal.
Image of page 20
Coupling receptors to enzyme action Receptor binding changes the probability of the “active” state.
Image of page 21

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

View Full Document Right Arrow Icon
Image of page 22
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