The Central Dogma of Molecular Biology and Its Limitations
Concept Map
Exploring the intricacies of post-translational modifications (PTMs), this overview delves into how PTMs, inteins, DNA methylation, and prions impact protein function and genetic expression. It challenges the traditional central dogma by revealing sophisticated genetic interactions and the dynamic regulation of phenotypes beyond DNA/RNA sequences.
Summary
Outline
Post-Translational Modifications and Protein Function
Post-translational modifications (PTMs) are critical biochemical processes that occur after a protein has been synthesized, where the protein's structure and function are altered by the addition or removal of functional groups or the cleavage of peptide bonds. These modifications can include phosphorylation, glycosylation, ubiquitination, and more, which can affect protein stability, localization, activity, and interactions with other molecules. PTMs add a layer of complexity to the central dogma of molecular biology, which traditionally describes the flow of genetic information from DNA to RNA to protein, by showing that the final protein product can be extensively modified and regulated after synthesis.Inteins and Protein Splicing
Inteins are protein sequences that are able to catalyze their own excision from a host protein and subsequently join the remaining portions, known as exteins, to form a functional protein. This process, called protein splicing, is a form of post-translational modification. Inteins sometimes contain a homing endonuclease or a maturase domain, which can facilitate horizontal gene transfer by inserting or correcting intein sequences in new locations within the genome. This activity demonstrates a direct role for proteins in the modification of genetic material, providing an exception to the central dogma's principle that information flows from nucleic acids to proteins but not in reverse.DNA Methylation and Gene Expression
DNA methylation involves the addition of methyl groups to the cytosine or adenine nucleotides of DNA, often leading to changes in gene expression. This epigenetic mechanism is catalyzed by enzymes known as DNA methyltransferases and can result in the silencing of genes. Methylation patterns can be heritable and play a role in development, genomic imprinting, and the suppression of transposable elements. While DNA methylation does not change the DNA sequence itself, it does alter how cells use that sequence, thereby influencing the central dogma by controlling the potential for gene expression prior to transcription.Prions and Protein-Based Inheritance
Prions are infectious agents composed solely of protein that can induce misfolding in normal, cellular prion proteins, leading to a cascade of misfolding and aggregation. This process can result in diseases such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. Prions challenge the central dogma by demonstrating a form of inheritance based on protein conformation rather than nucleic acid sequence. While prions do not encode genetic information or replicate in the manner of nucleic acids, they represent a non-traditional means of transmitting biological information, which can have profound effects on cellular function.Reevaluating the Central Dogma
The concept of natural genetic engineering, introduced by molecular biologist James A. Shapiro, posits that cells are capable of more sophisticated genetic manipulation than previously thought, including the ability to restructure their own genomes. This concept, along with the examples of post-translational modifications, inteins, DNA methylation, and prions, suggests that the central dogma, while useful, may not fully capture the complexity of genetic information flow and regulation. The central dogma, originally proposed by Francis Crick, is not incorrect but rather incomplete, as it does not account for these dynamic interactions between proteins and nucleic acids that can influence the phenotype beyond the direct sequence of DNA and RNA.
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Post-Translational Modifications
Types of PTMs
PTMs, such as phosphorylation and glycosylation, can alter a protein's structure and function
Effects of PTMs
Protein stability and localization
PTMs can affect a protein's stability and localization within a cell
Protein activity and interactions
PTMs can also impact a protein's activity and interactions with other molecules
Role of PTMs in the Central Dogma
PTMs add complexity to the central dogma by showing that proteins can be extensively modified and regulated after synthesis
Inteins and Protein Splicing
Definition and Function of Inteins
Inteins are protein sequences that can catalyze their own excision from a host protein, known as protein splicing
Intein Domains and Horizontal Gene Transfer
Inteins can contain domains that facilitate horizontal gene transfer by inserting or correcting intein sequences in new locations within the genome
Role of Inteins in the Central Dogma
Inteins demonstrate a direct role for proteins in modifying genetic material, challenging the central dogma's principle of information flow from nucleic acids to proteins
DNA Methylation and Gene Expression
Definition and Mechanism of DNA Methylation
DNA methylation involves the addition of methyl groups to DNA, often leading to changes in gene expression
Heritability and Functions of DNA Methylation
Heritability of Methylation Patterns
Methylation patterns can be heritable and play a role in development, genomic imprinting, and the suppression of transposable elements
Influence on Gene Expression
DNA methylation can alter how cells use genetic information, influencing the central dogma by controlling gene expression prior to transcription
Role of DNA Methylation in the Central Dogma
DNA methylation challenges the central dogma by showing that modifications to DNA can influence gene expression and phenotype
Prions and Protein-Based Inheritance
Definition and Mechanism of Prions
Prions are infectious agents composed solely of protein that can induce misfolding in normal, cellular prion proteins
Diseases and Implications of Prion Misfolding
Prion misfolding can lead to diseases such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, challenging the central dogma by demonstrating a form of inheritance based on protein conformation
Role of Prions in the Central Dogma
Prions represent a non-traditional means of transmitting biological information, challenging the central dogma's principle of information flow from nucleic acids to proteins
The Central Dogma of Molecular Biology and Its Limitations
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00
After a protein is synthesized, its structure and function may be changed through the addition or removal of ______ or the cleavage of ______.
functional groups
peptide bonds
01
______, ______, and ______ are examples of modifications that can influence a protein's stability, localization, activity, and interactions.
Phosphorylation
glycosylation
ubiquitination
02
Protein splicing process
Inteins catalyze their excision from a host protein, joining exteins to form a functional protein.
