Structural Biochemistry/Protein function/Conformational Selection

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Conformation Selection is when a dynamically fluctuating protein (ligand) binds to a protein and shifts the conformational ensemble towards a stabilized state. You may think that conformation selection and induced fit are the same, but induced fit only concerns about the interaction between a protein and its rigid binding partner. Recent studies and experiments are still trying to find a rigid distinction between the two.

Introduction[edit]

In the late-1990s, X-ray and cryo-electron microscope images, NMR data and kinetics studies were done by scientists to verify the 'lock and key' hypothesis. After years and years of work, models were presented to uncover the complexity of binding scenarios. The Koshland-Nemethy-Filmer (KNF) and the Monod-Wyman-Changeux (MWC) model described the allosteric effect on binding. Allosteric effect is when a ligand binds to a binding site, it induces a conformational change that affect binding ability of the other site. Recent experiments and data show that conformational selection is usually followed by this conformation change or conformation adjustment, thus making the distinction between the induced fit and the original conformation selection models more confusing.

The extended conformation selection model[edit]

The extended conformational selection model does not only show us that the conformations of the proteins change, but the energy of both binding proteins also changes. As the two proteins approach each other, the electrostatic force and hydrogen bonding change the energy content of the two proteins. These proteins can also undergo different conformational selection and adjustment steps to perform a particular function. These selections and adjustments are step-wise, with one follows another, and dependent, with one step affecting the next or further steps.

There are also a few factors that affect the conformation selection:

  1. Strength of interaction (ionic, hydrogen bond or dipole-dipole)
  2. Concentration of proteins
  3. Size difference (larger proteins often have higher flexibility)

Contributors to conformation changes[edit]

Over years and years of experiments, contributors to conformational changes are identified. The contributors are believed to play a vital role in protein's conformational changes. Transient Encounter complexes: these complexes are small (small contact area) and are hold by electrostatic forces. However, they cover a relatively large (~15%) surface area at the binding site. Anchor residues: they are in conformation that are similar to the final conformation after binding. They have a large contact area. Latch Residues: there residues are presented to stabilize the interaction between proteins. Protein segments: these segments amass kinetic energy and provide the energy for conformational changes. They are found to exchange up to 65% of their stored kinetic energy during conformational changes, which trigger the induced-fit effect and greatly contribute to the binding.

Large Conformation Changes[edit]

Ras proteins and protein kinases (guanine and adenine nucleotide triphosphatases) go through big conformational changes when a ligand binds in the course of their functions. Some new computer simulation methods are being combined with experiments to further our knowledge of conformational changes. What scientists refer to as a ‘conformational selection picture’ is surfacing where changes in the relative populations of known conformations can best explain the conformational switching activity of important proteins. [1]


Protein folding and binding[edit]

Over decades, scientists are trying to solve the protein folding problem. In order to thoroughly understand how proteins fold into 3D structure, scientists have to first discover the folding and unfolding of protein. Through experiments, there are a few essential studies that contribute to the biochemical society.

Temperature[edit]

Temperature affects the stability and folding of proteins. At high temperatures, scientists found that most proteins are unstructured. This is because, at high temperature, weak bonding such as ionic interaction and hydrogen bonding is broke apart. This decreases the induced-fit effect of the proteins and increase their conformational selection.

Chaperones[edit]

Chaperones aid the assembly of proteins and solve the problem of aggregation (proteins fold into a giant polymorphic aggregate species. A number of chaperones have the ability to unfold proteins and promote the binding of protein complexes.

Reference[edit]

Peter Csermely, Robin Palotai and Ruth Nussinov. Induced fit, conformational selection and independent dynamic segments: an

extended view of binding events. Trends Biochem Sci. 2010 Jun 10.

  1. Large conformational changes in proteins: signaling and other functions. Barry J. Grant, Alemayehu A. Gorfe, and J. Andrew McCammon.