Lac repressor: Difference between revisions

<StructureSection load='1osl_19_1l1m_9_morph.pdb' size='450' 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]].

Upon recognizing the specific operator sequence, the non-specific binding converts to <scene name='Lac_repressor/1l1m_ca_specific_bindiing/3'>specific binding</scene> (derived<ref name='alphac' /> from [[1l1m]], 20 [[NMR Ensembles of Models|NMR models]]). During this conversion, the hinge region changes from disordered loops to {{Template:ColorKey_Helix}} (<scene name='Lac_repressor/1l1m_ca_specific_bindiing/4'>highlight new helices</scene>), which bind to the minor groove of the DNA. As explained below, this binding stabilizes a '''kinked ("bent")''' <font color='#ae00ff'><b>DNA double helix</b></font> conformation. What percentage of time this DNA sequence spends in  a kinked state, in the absence of bound lac repressor protein, is not known, but it may be a significant percentage (see next section below). <scene name='Lac_repressor/1l1m_ca_specific_bindiing/6'>Animating</scene> these 20 NMR models can be compared with the animation of the non-specific binding.  See [[Lac repressor morph methods]]. {{Template:Button Toggle Animation}}

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.

[[Lac repressor 3D structures]]