Lac repressor: Difference between revisions

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__NOTOC__
__NOTOC__
<StructureSection load='1osl_19_1l1m_9_morph.pdb' size='450' side='right' scene='Morphs/1osl_19_1l1m_9_morph/2' caption=''>
<StructureSection load='' size='375' side='right' scene='Morphs/1osl_19_1l1m_9_morph/2' caption=''>
[[Morphs|Morph]] of the '''lac repressor''' complexed with DNA showing the differences between non-specific binding (straight DNA) vs. specific recognition of the operator sequence (kinked DNA). Whether the binding kinks the DNA, or simply stabilizes a pre-existing kink, is unknown. [[#Specific Binding| Details Below]].
[[Morphs|Morph]] of the '''lac repressor''' complexed with DNA
 
(<scene name="Morphs/1osl_19_1l1m_9_morph/2">restore initial scene</scene>) After displaying interactive model: {{Template:Button Toggle Animation2}}
showing the differences between non-specific binding (straight DNA) vs. specific recognition of the operator sequence (kinked DNA). Whether the binding kinks the DNA, or simply stabilizes a pre-existing kink, is unknown. [[#Specific Binding| Details Below]].
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==What is the lac repressor?==
==What is the lac repressor?==
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====DNA Kinks====
====DNA Kinks====
Strictly speaking, ''bends'' in DNA are distinguished from ''kinks''. DNA is said to be '''kinked''' when the stacking contact between two adjacent base pairs is disrupted<ref name="rohsrev2010" />. The DNA on either side of a kink may be straight or bent. A <scene name='Lac_repressor/Kink/2'>kink occurs in the complex between the lac repressor and specific DNA</scene>: a single CpG base pair is partially separated from the adjacent CpG base pair. <scene name='Lac_repressor/Kink/3'>Zoom in</scene>. Pyrimidine-purine base pairs have the weakest stacking interactions, and are most susceptible to kinking<ref name="rohsrev2010" />. In the complex of lac repressor with specific DNA, <scene name='Lac_repressor/Kink_leu56/1'>two leucines (Leu56)</scene> are partially interchalated between the separated CpG base pairs, which helps to stabilize the kink. It may often be the case that sequence-dependent kinks and bends are present in DNA prior to the binding of protein<ref name="rohsrev2010" />. DNA structure is dynamic. For example, recently Hoogsteen base pairing was observed to occur transiently in equilibrium with Watson-Crick base pairing<ref>PMID: 21270796</ref> (See ''News & Views''<ref>PMID: 21350476</ref>). Also, the binding of p53 to some but not all DNA sequences stabilizes Hoogsteen (rather than Watson-Crick) base pairing<ref>PMID: 20364130</ref>. Thus, the "bending" (actually kinking) depicted in '''the morph on this page may give the wrong impression''': lac repressor binding may simply stabilize a kink (or transient kink) that pre-existed in the cognate DNA sequence.
Strictly speaking, ''bends'' in DNA are distinguished from ''kinks''. DNA is said to be '''kinked''' when the stacking contact between two adjacent base pairs is disrupted<ref name="rohsrev2010" />. The DNA on either side of a kink may be straight or bent. A <scene name='Lac_repressor/Kink/2'>kink occurs in the complex between the lac repressor and specific DNA</scene>: a single CpG base pair is partially separated from the adjacent CpG base pair. <scene name='Lac_repressor/Kink/3'>Zoom in</scene>. Pyrimidine-purine base pairs have the weakest stacking interactions, and are most susceptible to kinking<ref name="rohsrev2010" />. In the complex of lac repressor with specific DNA, <scene name='Lac_repressor/Kink_leu56/1'>two leucines (Leu56)</scene> (if scene is blank,<jmol>
  <jmolLink>
    <script> model 0;</script>
    <text>please click</text>
  </jmolLink>
</jmol>)<!--(<font color="red">Sorry, this scene is temporarily broken.</font>)--> are partially intercalated between the separated CpG base pairs, which helps to stabilize the kink. It may often be the case that sequence-dependent kinks and bends are present in DNA prior to the binding of protein<ref name="rohsrev2010" />. DNA structure is dynamic. For example, recently Hoogsteen base pairing was observed to occur transiently in equilibrium with Watson-Crick base pairing<ref>PMID: 21270796</ref> (See ''News & Views''<ref>PMID: 21350476</ref>). Also, the binding of p53 to some but not all DNA sequences stabilizes Hoogsteen (rather than Watson-Crick) base pairing<ref>PMID: 20364130</ref>. Thus, the "bending" (actually kinking) depicted in '''the morph on this page may give the wrong impression''': lac repressor binding may simply stabilize a kink (or transient kink) that pre-existed in the cognate DNA sequence.


====DNA Bends====
====DNA Bends====
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[[Category:Topic Page]]
[[Category:Topic Page]]
[[Category: BioMolViz]]
[[Category: Molecular Dynamics]]

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

Eric Martz, Eran Hodis, David Canner, Michal Harel, Alexander Berchansky, Joel L. Sussman, Henry Jakubowski, Karsten Theis, Jaime Prilusky