Lecture 6: Gene Functions: Proteins and Enzymes Part 3 PDF

Lecture 6 Gene Functions: Proteins and Enzymes Part 3 Model of the operon and its relation to the regulator gene. E. Regulation of Gene Action Genetic information transfer is best illustrated by the Central Dogma of Molecular Biology. However, information...

Lecture 6 Gene Functions: Proteins and Enzymes Part 3 Model of the operon and its relation to the regulator gene. E. Regulation of Gene Action Genetic information transfer is best illustrated by the Central Dogma of Molecular Biology. However, information is only a part of the problem; gene action also needs to be regulated. Embryonic Development Embryonic development, for example, is a highly regulated activity where different genes exert their functions at specific times and in specific amounts. This requires some mechanism for turning the genes on and off and for regulating their level of production.  Another example is the appearance of inherited traits at various stages of development: the gene for Tay Sachs disease is expressed in the first few years of life; that for the X-linked muscular dystrophy produces its damage on teenagers; and Huntington's disease starts in middle adult life.  Furthermore, different species often have very similar protein compositions: humans and chimpanzees are alike for more than 99% of amino acid sites in corresponding proteins. This suggests that the differences may be more on regulating the amounts of different proteins rather than on the production of different types of proteins. Subtopics: 1. Regulation of gene action in prokaryotes 1.1. Definition of Terms 1.2. Negative Transcriptional Control 1.2.1. The Lactose Operon (Ariaso, Ana Rose) 1.2.2. Tryptophan Operon (Cojeda, Princess Dawn) 1.3. Positive Transcriptional Control 1.3.1. The arabinose Operon (Claros, Charlene) 2. Regulation of gene action in eukaryotes 2.1. The Davidson-Britten Model (Montallana, Mariel) 2.2. Control of specific gene expression (Badanoy, Angel) 1.1. Definition of Terms a) Constitutive enzymes are those The constitutive synthesized at constant rates and in enzymes are constant amounts, regardless of the metabolic state of the cell, e.g., enzymes of produced all the glycolytic pathway. time, whereas, b) Inducible enzymes are those that are inducible enzymes normally present in trace amounts but their are synthesized concentrations can quickly increase a only under certain thousand fold or more when their substrate is present in the medium, particularly when conditions or on this substrate is the only carbon source of requirement. the cell. c) Coordinate induction refers to the induction of a group of related enzymes or proteins by a single inducing agent. d) Coordinate repression refers to the repression of a group of enzymes catalyzing a sequence of consecutive biosynthetic reactions. Coordinate repression is ordinarily evoked by the end product of the series of biosynthetic reactions catalyzed by the repressed enzymes. For this reason it is called end product repression. e) Catabolite repression refers to enzyme repression signalled by the increase in the intracellular level of glucose or some catabolite derived from glucose. f) Structural gene is defined as a gene that carries the message for the amino acid sequence of a specific protein. g) Regulatory gene (i gene) codes for the amino acid sequence of a specific protein called the repressor; this gene determines whether of not the structural genes will be transcribed. h) Operator or o locus is the site in the DNA to which the repressor molecule binds. When the repressor is bound to the o locus, the transcription of the structural gene is prevented. i) Promoter or (p) is the site in the DNA which the DNA-directed RNA polymerase recognizes as an initiation signal to indicate where transcription of mRNA begins. j) Repressor is the specific protein coded for by the regulatory gene. k) Co-repressor is a small molecule that binds the aporepressor to activate the aporepressor (in cases where ordinarily the aporepressor is in an inactive state). A repressor that binds with a co-repressor is termed an aporepressor or inactive repressor. l) Inducer is a small molecule that stimulates synthesis of specific proteins by binding with the repressor to form a repressor-inducer complex incapable of binding the o locus. m) Operon is defined as a group of functionally related structural genes mapping close to each other in the chromosome and the adjacent transcriptional control sites. n) Negative control occurs when the inducer binds to the repressor, thereby rendering it unable to bind to the operator gene. o) Positive control occurs when the inducer binds to the repressor and imparts to it the ability to bind to the positive activator gene. p) Positive activator gene (PAG) is the binding site for the regulatory protein known as an activator. This protein binds specifically to the PAG opening it to the passage of RNA pol, thereby increasing transcription of the operon. 1.2 Negative Transcriptional Control The negative Transcriptional system is characterized by the production of a repressor protein by the regulatory gene. The system may be either inducible or repressible. 1.2. Negative Transcriptional Control 1.2.1. The Lactose Operon (Ariaso, Ana Rose) 1.2.2. Tryptophan Operon (Cojeda, Princess Dawn) REPORTER: ARIASO, ANA ROSE REPORTER: COJEDA, PRINCESS DAWN 1.2.2. Tryptophan (trp) Operon: A Repressible Negative Transcriptions Control System Bacteria such E. coli need amino acids to survive - because like us, they need to build proteins. Tryptophan is one of the amino acids they need and ingested from the environment. If tryptophan is available in the in the environment, E. coli will take it up and used it to build proteins. However, they can make their own tryptophan using enzyme that are encoded by five genes - located next to each other on the Tryptophan (trp) operon. The trp operon has an attenuator region: a region of the mRNA leader neat gene E where transcription usually terminates in the absence of regulatory input.  Figure: The trp operon: The five genes that are needed to synthesize tryptophan in E. coli are located next to each other in the trp operon. When tryptophan is plentiful, two tryptophan molecules bind the repressor protein at the operator sequence. This physically blocks the RNA polymerase from transcribing the tryptophan genes. When tryptophan is absent, the repressor protein does not bind to the operator and the genes are transcribed. https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/07%3A_Microbial_Genetics/7.18%3A_Global_Regulatory_Mechanisms/7.18B%3A_The_trp_Operon_-_A_Repressor_Operon To Review : Tryptophan is low Tryptophan is high Inactive repressor Active repressor Trp genes expressed Trp are not expressed. Trp produce 1.3. Positive Transcriptional Control System Positive control means that the regulatory gene product stimulates transcription; it is an expressor rather than a repressor of transcription. The role of the active repressor protein is to increase the recognition of the operon’s promoter(s) by RNA polymerase or to enable the RNA polymerase to continue transcription past the attenuator. 1.3. Positive Transcriptional Control 1.3.1. The arabinose Operon (Claros, Charlene) REPORTER: CLAROS, CHARLENE 1.3.1. The Arabinose Operon: An Inducible Positive Transcriptional System The arabinose operon specifies the enzymes that catalyze the conversion of L-arabinose to D-xylulose. The arabinose operon regulates gene expression for breaking down arabinose when glucose is absent, similar to the lactose operon. The genes and their products are illustrated in Figure 6-17.  1.3.1. The Arabinose Operon: An Inducible Positive Transcriptional System In the absence of arabinose (inducer), the ara C protein acts as a repressor. This protein exists in two conformations, P_{1} and P_{2} P_{1} is a repressor interacting with an operator region adjacent to the initiator. The presence of arabinose removes P_{1} from the operator and shifts the equilibrium in favor of P_{2} which binds to the initiator region allowing expression of the operon. At least three operons in E. coli - those involved in the catabolism of maltose, rhamnose and arabinose regulated. are positively 🍬 Sugar Preference: Bacteria prefer glucose but switch to arabinose when glucose is unavailable. 🔄 Operon Structure: Consists of regulatory regions, operators, and structural genes (araB, araA, araD). 🚫 Repressor Role: ARA C acts as a repressor, preventing transcription when arabinose is absent. ✅ Activator Function: Presence of arabinose converts ARA C from a repressor to an activator, enabling transcription. 🔗 Transcription Process: RNA polymerase binds to the promoter when ARA C is inactive, leading to enzyme production. 🔄 Metabolism Pathway: Enzymes break down arabinose into simpler sugars for energy production. Key Ins i ghts 🧬 Op e ron Si m i l ar i ti e s : Th e arab i n os e op e ron s h are s str u c tu ral an d f u n c ti on al s i m i l ar i ti e s w i th th e l ac tos e op e ron , hi ghl i ghti ng a com m on re gul ator y m e c hani s m i n bac te r i a. Thi s s i m i l ar i ty unde rs core s the eff i c i e nc y of ge ne re gul ati on i n re s pons e to e nvi ronm e ntal s ugars. 🍬 Nutr i ti onal Fl ex i bi l i ty: Bac te r i a’s abi l i ty to sw i tc h f rom gl ucos e to arabi nos e de m onstrate s the i r adaptabi l i ty i n nutr i e nt- s carc e e nvi ronm e nts , al l ow i ng s ur vi val i n di ve rs e condi ti ons. Thi s f l ex i bi l i ty i s c r uc i al for m i c robi al s ur vi val and grow th. 🔄 G e n e Str u c tu re : Th e arab i n os e op e ron contai n s e s s e nti al re gu l ator y e l e m e nts (op e rators an d re p re s s or p rote i n s ), w h i c h are c r i ti cal for pre c i s e control ove r ge ne expre s s i on, e ns ur i ng that e nzym e s are produc e d onl y w he n ne e de d. Prope r ge ne re gul ati on i s vi tal i n m etabol i c pathways. 🚫 Re pre s s i on M e c hani s m : ARA C ’s rol e as a re pre s s or i l l ustrate s how bac te r i a preve nt unne c e s s ar y e ne rgy expe ndi ture w he n arabi n os e i s not avai l abl e , s howcas i ng an eff i c i e nt re s ourc e m anage m e nt strate gy. Thi s m e c hani s m i s f undam e ntal for c e l l ul ar e ne rgy con s e r vati on. ✅ Ac ti vator Transfor m ati on: The conve rs i on of ARA C f rom a re pre s s or to an ac ti vator i n the pre s e nc e of arabi nos e exe m pl i f i e s a s ophi sti cate d re gul ator y sw i tc h that opti m i ze s ge ne expre s s i on bas e d on nutr i e nt avai l abi l i ty. Thi s dynam i c re gul ator y sw i tc h i s e s s e nti al for m etabol i c eff i c i e nc y. 🔗 Tran s c r i pti on al C ontrol : Th e ab i l i ty of RNA p ol ym e ras e to tran s c r i b e str u c tu ral ge n e s w h e n ARA C i s i n ac ti ve h i gh l i ghts th e ope ron’s f u nc ti on i n re s pondi ng to e nvi ronm e ntal c hange s , fac i l i tati ng qui c k adaptati on to avai l abl e re s ourc e s. Thi s re s pons i ve ne s s i s key to bac te r i al s ur vi val. 🔄 M etab ol i c Prod u c t Pathway: Th e b re akd ow n of arab i n os e i nto x yl u l os e 5- phos phate by the ope ron’s e nzym e s i l l ustrate s th e i nte rcon n e c te d n e s s of m etab ol i c p athways , d e m on strati n g h ow b ac te r i a eff i c i e ntl y u ti l i ze avai l ab l e s u gars for e n e rgy prod uc ti on. Thi s pathway i s c r uc i al for m ai ntai ni ng c e l l u l ar e ne rgy b al anc e. 2. Regulation of gene action in eukaryotes 2.1. The Davidson-Britten Model (Montallana, Mariel) 2.2. Control of specific gene expression (Badanoy, Angel) REPORTER: MONTALLANA, MARIEL THE DAVIDSON-BRITTEN MODEL PRESENTED BY: MARIEL. MONTALLANA FOUR TYPES OF GENES Sensor Gene Receptor Site these are signal receiving genes provides a link between integrator gene and producer gene Integrator Gene Structural Gene start transcription after receiving starts transcription after receiving signal from sensor game signal from receptor gene REPORTER: BADANOY, ANGEL 2.2 Control of Specific Gene Expression by Hormones What do hormones have to do with gene regulation?  What are Hormones? Hormones are chemical messengers that allow different parts of our bodies to communicate. They are often released in response to a signal from our environment that our body needs to respond to. When a cell detects a message in the form of a hormone, it changes its activities based on that particular message. One of the ways cells change their activities is by adjusting which genes are on or off. What do hormones have to do with gene regulation? All of our cells contain all of our genes, but not all of our genes are turned on all the time in every cell. This is why an eye cell and a lung cell can contain the same genes, but look and act very differently!  Hormones Genes can also differ in how much they This ability to adjust how much are turned on. You can think of this a gene is expressed allows our like a thermostat rather than an “on- bodies to respond to off” switch. environmental changes and maintain balance as we go about our day. Our cells have many ways to regulate gene expression, and one of these is by responding to hormones. David-Britten Model This model suggests that hormones can influence gene expression by interacting with receptor proteins. These hormone-receptor complexes can either activate or repress specific genes. When hormones bind to The overall model highlights their receptors, they can act the role of external signaling as transcription factors or molecules (like hormones) in influence transcription regulating gene expression in factors, ultimately affecting response to environmental or the transcription of target physiological changes. genes.  Did you know? In 1974, Stein, Spelsberg and Kleinsmith proposed a model of gene regulation, particularly focusing on steroid hormones and their role in controlling gene expression. Their proposed regulatory sequence follows these general steps: 1. Steroid Hormone Binding A steroid hormone (such as estrogen or testosterone) diffuses into the cell due to its lipophilic nature and binds to a specific intracellular receptor protein. 2.Hormone-Receptor Complex Formation Once the steroid hormone binds to its receptor, a hormone-receptor complex is formed. This complex undergoes a conformational change, allowing it to be activated. Their proposed regulatory sequence follows these general steps: 3.Translocation to the Nucleus The activated hormone-receptor complex then moves into the nucleus of the cell. 4. Binding to DNA Inside the nucleus, the hormone-receptor complex binds to specific DNA sequences known as hormone response elements (HREs), which are located near or within the promoter regions of target genes. Their proposed regulatory sequence follows these general steps: 5.Transcription Activation Binding to the HREs facilitates the recruitment of RNA polymerase and other transcription factors, leading to the initiation of transcription of the target gene. 6. mRNA Production and Protein Synthesis Once transcription is activated, mRNA is produced, exits the nucleus, and is translated into proteins in the cytoplasm. These proteins can have various biological effects, depending on the specific genes activated.  Conclusion Hormones are essential regulators of gene expression, affecting various physiological processes such as growth, metabolism, and stress response. In conclusion, the regulatory model proposed by Stein, Spelsberg, and Kleinsmith in 1974 highlights a crucial mechanism of steroid hormone action on gene expression. The process begins with a steroid hormone (H) binding to its specific cytoplasmic receptor ®, activating the receptor (forming H-R’) to allow its entry into the nucleus. Once inside the nucleus, the H-R' complex binds to hormone response elements (HREs) on DNA, regulating gene transcription and ultimately influencing protein synthesis.  Thanks! Do you have any questions? CREDITS: This presentation template was created by Slidesgo, and includes icons by Flaticon, and infographics & images by Freepik