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Showing posts with the label Cell Surface Receptors

Explain the downstream signalling of RTKs

Receptor Tyrosine Kinases (RTKs)  are special types of transmembrane receptors that help the cell to receive and process external signals like growth factors, insulin and other peptide hormones. These signals control very important cellular processes like cell division, cell growth, metabolism, and survival. When a signal molecule binds to the RTK, it activates a cascade of events inside the cell. This entire process is known as  downstream signalling of RTKs. There are five main steps in the downstream signalling of RTKs. The signal starts from ligand binding and proceeds until intracellular kinases activate target proteins. Step 1: Ligand Binding and Receptor Dimerisation The process begins when an extracellular signalling molecule such as epidermal growth factor (EGF) or insulin binds to the extracellular domain of RTK. Once the ligand binds, it causes dimerisation of the two RTK monomers. This means two receptor molecules come together and form a dimer. This dimerisation b...
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Describe the downstream signalling of GPCRs

G-protein-coupled receptors (GPCRs)  are  transmembrane receptors  that help the cell to receive signals from the external environment and pass them inside the cell. These signals can be in the form of hormones, neurotransmitters and sensory stimuli like smell or light. When a signal binds to the receptor, it activates the intracellular machinery to start a process known as  downstream signalling.  This signalling starts after the receptor is activated and ends when the final cellular response begins. There are five main steps in the downstream signalling of GPCRs, starting from ligand binding and ending with kinase activation. Step 1: Ligand Binding and GPCR Activation The first step begins when an external ligand like  epinephrine or serotonin  binds to the extracellular part of the GPCR. This binding causes a conformational change in the structure of the receptor. Because of this shape change, the cytoplasmic portion of the GPCR becomes able to inte...
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How does MAPK get activated?

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Mitogen-activated protein kinases (MAPKs)  are essential enzymes that play a crucial role in regulating a wide range of cellular activities, such as cell growth, differentiation, apoptosis and responses to stress signals. The activation of MAPK occurs through a complex signaling cascade that involves multiple stages and various proteins working in a precise sequence. There are three main types of MAPK pathways: the  ERK  (extracellular signal-regulated kinase) pathway, the  JNK  (c-Jun N-terminal kinase) pathway and the  p38 MAPK  pathway. Despite differences, these pathways follow a common set of activation steps. The activation of MAPK involves a sequence of events, starting from the binding of an external signal to a cell surface receptor and ending with the regulation of gene expression in the nucleus. The process can be divided into several stages, as follows: 1. Receptor Activation: The First Step in the MAPK Cascade MAPK signaling begins when an...
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Define GEFs

GEFs means  Guanine nucleotide Exchange Factors.  These are special types of regulatory proteins that are responsible for the activation of  small GTP-binding proteins (also called as GTPases).  These small GTPases, like  Ras, Rho, Rab, Ran and Arf  are molecular switches which are very important in many cellular processes like signal transduction, vesicle trafficking, cytoskeleton regulation and cell cycle control. GTP-binding proteins always exist in two forms. When they are  bound to GDP, they are inactive.  When they are  bound to GTP, they are active.  But GDP does not leave the inactive G-protein by itself because it binds tightly. Here, GEFs play an important role. GEFs help the GTPase protein to release GDP and allow a new GTP to bind. This switching from GDP to GTP turns on the GTPase. For example,  Ras protein  is a small GTPase involved in growth factor signaling. When a growth factor binds to its receptor on the mem...
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Define Adaptor proteins

Adaptor proteins are  non-enzymatic intracellular proteins  that play a critical role in  cellular signaling.  They act as  linkers, bridges, or scaffolds  by connecting cell surface receptors to downstream signaling molecules, facilitating the formation of  signaling complexes.  Although adaptor proteins do not possess  enzymatic activity,  they are essential in transmitting signals by binding to specific sites on other proteins. This binding ensures the accurate transmission of signals, which is crucial for regulating various cellular functions, such as growth, differentiation, immune responses and apoptosis. In this way, adaptor proteins play a fundamental role in maintaining cellular communication and ensuring signal pathway specificity. Most adaptor proteins contain specialized structural domains, including  SH2  (Src Homology 2),  SH3  (Src Homology 3),  PTB  (Phosphotyrosine Binding) and  PDZ ...
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What are the different ways in which GPCR regulates cellular functions upon hormone binding?

G-protein-coupled receptors (GPCRs) are a large family of membrane receptors that sense extracellular signals such as hormones, neurotransmitters and sensory stimuli. Upon ligand (hormone) binding, GPCR undergoes a conformational change and activates  heterotrimeric G-proteins  by promoting the exchange of GDP for GTP on the  Gα subunit.  The GTP-bound Gα subunit and Gβγ dimer then dissociate and modulate various downstream effectors inside the cell. GPCRs regulate cellular functions through the following four main mechanisms: i) By Activating Protein Kinase A (PKA) Many hormones like epinephrine act via Gs-protein-coupled receptors. The activated Gαs subunit stimulates the enzyme adenylyl cyclase, which converts ATP to cyclic AMP (cAMP). The increased levels of cAMP then activate protein kinase A (PKA). Activated PKA phosphorylates various target proteins, enzymes and transcription factors, leading to diverse cellular responses like increased heart rate, glycogen br...
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What is the role of RGS proteins?

Regulators of G-protein signaling (RGS) proteins are crucial components in the regulation of  G-protein-coupled receptor (GPCR) signaling.  GPCRs are involved in the transmission of extracellular signals into cells and are essential for controlling a variety of biological processes, including growth, metabolism, immune responses and neurotransmission. When a ligand binds to a GPCR, it activates the G-protein by promoting the  exchange of GDP for GTP on the Gα subunit,  causing downstream signaling. However, the cell must be able to terminate this signal appropriately to maintain homeostasis and avoid excessive or prolonged signaling, which can lead to disease states like cancer, cardiac arrhythmias, or neurological disorders. This is where RGS proteins come into play. RGS proteins act as critical regulators that accelerate the deactivation of the G-protein, ensuring that the signal is  turned off  at the right time. Their main function is to enhance the GTP...
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What would happen if there were substances that could bind to Ga subunits just like GTP does, but could not be hydrolysed by the intrinsic GTPase?

If substances were present that could bind to the Gα subunits just like GTP does, but could not be hydrolyzed by the intrinsic GTPase activity, it would lead to a  persistent activation of the G-protein signaling pathway.  This is because the normal process of signal termination in G-protein signaling involves GTP hydrolysis by the intrinsic GTPase activity of the Gα subunit. When GTP is hydrolyzed to GDP, the Gα subunit becomes  inactive,  effectively terminating the signaling cascade. However, if a substance mimics GTP binding but does not undergo hydrolysis, the Gα subunit would remain in its active GTP-bound form indefinitely. This leads to prolonged activation of downstream signaling pathways, such as the activation of second messengers like cAMP, DAG and IP3, and the continuous activation of effector proteins. Such persistent signaling can result in abnormal cellular responses, as the cell remains in a state of continuous  "activation"  without return...
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What is the difference between the classical concept and the modern concept of genes?

The concept of the gene has evolved from a simple unit of heredity to a complex molecular entity. During  Mendel's  time, genes were understood only through the inheritance of physical traits. This formed the  classical concept.  With the discovery of DNA, its double helix structure and the development of molecular biology, the gene is now defined by its chemical structure and functional properties. This is known as the  modern concept. For understanding the difference between the classical and modern concept of genes, the following criteria are used: 1. Based on Definition or Concept Classical Concept:  Gene was defined as an abstract unit of heredity responsible for controlling a  single trait.  It was known through breeding experiments and inheritance patterns. Modern Concept:  A gene is a segment of DNA that contains the information to produce a functional product, either a protein or an RNA. It is both a structural and functional unit of...
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Why is the frequency of double crossover overly low?

The frequency of double crossover is usually much lower than expected. This is mainly due to a natural genetic mechanism called interference, which controls the distribution of crossover events during meiosis. Crossover is essential for genetic recombination but is also tightly regulated to prevent instability in the genome. The lower frequency of double crossovers can be explained by the following reasons: 1. Physical Constraints of Chromosomes Chromosomes have a limited length and physical structure. When a crossover happens at one region of a chromosome, the local chromatin structure and spatial arrangement become less favorable for another crossover nearby. This physical limitation reduces the chance of two crossovers occurring very close to each other on the same chromosome segment. 2. Crossover Interference One of the main reasons for reduced double crossovers is the phenomenon called  interference.  Interference is the effect where the occurrence of one crossover decrea...
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What is gene mapping? How do the linked genes help in gene mapping?

Gene mapping is the method used to determine the location of genes on a chromosome and the distance between them. It helps in identifying the exact position of a gene responsible for a particular trait or disease. The concept started with the work of  Thomas Hunt Morgan  in the early 1900s when he studied Drosophila melanogaster (fruit fly) and observed that some traits are inherited together. This was because the genes responsible for those traits were located close to each other on the same chromosome. This phenomenon is known as  linkage. There are two main types of gene mapping: 1. Genetic Mapping (Linkage Mapping): Genetic mapping uses the frequency of recombination or crossing over between genes to estimate their distance on a chromosome. It gives a  relative position of genes rather than their exact physical location. 2. Physical Mapping Physical mapping uses molecular biology techniques to determine the exact nucleotide sequence of DNA and the exact physical ...
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The First Living Molecule

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The question of which molecule can be considered the "first living molecule" is complex and doesn't have a definitive answer. This depends on whether we are discussing the molecule that played a key role in the  origin of life  or the  first organic molecules  that formed chemically on early Earth. While  RNA is considered crucial in the emergence of life,   amino acids were likely the first molecules to appear in Earth's primordial environment.  Understanding these distinctions clarifies the discussion about whether RNA or amino acids came first. Introduction: 1. According to the Origin of Life: In the context of the origin of life, the first molecule is likely  RNA.  RNA's ability to store genetic information and catalyze its own replication (acting as both a genetic material and an enzyme) gives it a key role in early life. The  RNA World Hypothesis  suggests that RNA existed before amino acids or proteins, as it could facilitat...
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What is the difference between regulatory gene and structural gene?

Genes are basic units of heredity that carry instructions for the development and functioning of living organisms. Among various types of genes,  regulatory genes  and  structural genes  are essential for the proper functioning of cells, but their roles are quite different. Regulatory genes mainly control other genes, while structural genes directly code for proteins that form the body's structures or perform specific functions. To understand their differences clearly, we will compare them based on important criteria. 1. Based on Function The main function of  regulatory genes  is to control or regulate the expression of other genes. They produce regulatory proteins, such as repressors or activators, that influence whether structural genes are switched on or off. This control mechanism ensures that genes are expressed only when needed. In contrast,  structural genes  code directly for proteins or RNA molecules that are involved in building cellula...
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Subatomic Particles

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Atoms are the basic units of matter and are made up of smaller components called subatomic particles. There are many types of subatomic particles known to science, but in the context of basic atomic structure, only three are considered most important: electrons, protons and neutrons. These three particles differ in their location, charge and mass. Together, electrons, protons and neutrons form the complete structure of atoms. Their arrangement and interaction define the atom's properties, chemical behavior, and participation in physical and chemical processes. These subatomic particles laid the foundation of modern atomic theory and quantum chemistry. 1. Electron Electrons are negatively charged subatomic particles. They are extremely small in mass and are found outside the nucleus of the atom in specific regions called orbitals or shells. The charge of an electron is −1  and its mass is approximately 1/1836 of a proton or neutron, which is around 9.1 × 10⁻³¹ kg, meaning it is n...
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Differentiate between linked genes and unlinked genes?

Genes are specific sequences of DNA that code for proteins and determine traits in an organism. During the study of chromosomal theory of  inheritance, scientists found that not all genes behave the same way. Some genes tend to be inherited together while others assort independently. Based on this behavior, genes are divided into two types:  linked genes and unlinked genes.  This concept is very important in genetics because it helps in understanding how traits are passed on and how gene positions can be mapped on chromosomes. These differences are explained based on specific criteria: 1. Based on Chromosomal Location Linked genes  are located close to each other on the same chromosome. Because of their close physical proximity, they usually move together during meiosis and are inherited as a group. For example: In Drosophila melanogaster (fruit fly), the genes for eye color and wing shape are located close to each other on the X chromosome. Unlinked genes  are ...
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Can marriage between two albinos produce children with normal pigmentation?

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Albinism is a genetic condition where a person lacks melanin, the pigment responsible for the colour of skin, hair and eyes. It is usually inherited in an autosomal recessive manner. The most common forms of albinism, such as oculocutaneous albinism (OCA), are caused by mutations in genes like TYR, OCA2, TYRP1 etc. For a person to show albinism, they must inherit two copies of the defective allele, one from each parent. This means the genotype of an albino individual is generally homozygous recessive (aa). If both parents are albino due to mutations in the same gene, then their genotype would be aa, and the only gametes they can produce will carry the a allele. When we perform a cross: Parent 1: aa × Parent 2: aa Gametes: a a All children will also be aa, hence all children will be albino. Therefore, if both parents are albino due to the same gene, they cannot produce a normally pigmented child. However, in rare cases, albinism can result from mutations in different genes in e...
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Define and distinguish sex-linked, sex-limited and sex-influenced characters

In genetics, traits can be influenced or expressed differently depending on the sex of the individual. Some traits are linked to sex chromosomes, while others are affected by hormonal or physiological differences between males and females. To describe these traits more precisely, geneticists use three main terms:  sex-linked, sex-limited and sex-influenced traits.  Although these terms may sound similar, they refer to different types of genetic expression related to sex. Understanding the distinction among these three is important for grasping how certain traits are inherited and expressed differently in males and females. 1. Sex-linked characters: These are traits controlled by genes that are located on the  sex chromosomes,  usually on the X chromosome in humans. Because males have only one X chromosome (XY) and females have two (XX), the pattern of inheritance and expression is different in both sexes. Most sex-linked traits are X-linked, and very few are Y-linked...
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Give two examples of gene interaction resulting in the formation of structural proteins

Gene interaction refers to a situation where two or more genes influence the  same trait.  In the case of structural proteins, sometimes the final functional protein is not made from a single gene product but is the result of the combination of different polypeptides produced by different genes. Such interaction is especially important in the formation of complex structural proteins that require the association of multiple chains to become functional. Two good examples of this kind of gene interaction are seen in  haemoglobin and MHC (Major Histocompatibility Complex) molecules. 1. Haemoglobin (HbA) Haemoglobin is the oxygen-carrying protein found in red blood cells. The adult type of haemoglobin, called  HbA,  is a tetramer made up of two  alpha-globin chains and two beta-globin chains.  These chains are coded by different genes: The alpha-globin gene is located on  chromosome 16. The beta-globin gene is located on  chromosome 11. Both these...
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