Protein Recognition ofGenesBIBC 100How Proteins recognizeGenes• Most genes are silent, unlessspecifically turned onDNA RNA(Switch = Protein)TranscriptionFACTORGene Protein ActivatorRepressorCan be regulated by small moleculeGene Activators andRepressors• Main Controls of– Growth– Differentiation– OncogenesisSpecificityRecognitionAffinityDNA-ProteinActivators andRepressorsLOCKNucleotideBasesequenceDNAKEYProtein MotifI. Helx-Turn-HelixI. Pro:HTH(Dimer)II. EU: Homeodomaine(Monomer)Both: Metal FreeII. Zinc-StabilizedI. Helix-turn- b-sheetIII. Luecine-ZipperAct.Rep.DNA: Where?• Only the edges of thenucleotides are accessible to thesolvent or to protein, primarilyin the major groove of the DNAdouble helixProtein: How?• Protruding groups from proteinsurface to contact nucleotides atbase of groove• Motifs:– Helix-turn-Helix– Zinc Finger Protrusion– Leucine ZipperFor Bacterial HTH1. DNA is distorted2. Protein is dimeric3. H-bonds between sugar-phosphatebackbone and protein anchor DNA– protein4. Sequence-specific recognitionbetween DNA bases and a-helix5. Recognition helices in dimer areseparated 34Å apart, i.e. one turnof B-DNA6. If one helix binds to major groove,the second binds (34Å) to majorgroove one turn away7. Allosteric effectors…Allosteric Effectors• Small molecules• Act at a distance of recognition helix• Produce a conformational change =>switch• E.g. Trp repressor (image 4)Inactive Activetrpd≤29Å d=34ÅRecognition Helix (image 7)• CAP- cyclic
View Full Document
Unlocking...