membrane bound protein

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Consider the signaling pathway initiated by insulin receptor activation. If a cell line expressed a mutant IRS-1 protein lacking the SH2 domain binding site, what would be the MOST likely downstream effect?

Uncontrolled activation of GSK3.
Enhanced translocation of GLUT4 to the plasma membrane. (correct)
Failure to activate PI-3K.
Increased conversion of PIP2 to PIP3.

In the context of reversible phosphorylation as a biological signaling mechanism, which statement BEST describes the functional consequence of kinase activity?

It invariably leads to enzymatic activation by altering protein quaternary structure.
It modulates enzymatic activity, tertiary, and quaternary structure by phosphorylating serine, threonine or tyrosine residues.
It exclusively targets histidine residues to modulate protein-protein interactions.
It exclusively targets serine residues to modulate protein-protein interactions. (correct)

A researcher discovers a novel integral membrane protein. Topological analysis reveals that the N-terminus is located in the cytoplasm, and the protein contains a single transmembrane helix followed by a large extracellular domain with several glycosylation sites. According to established membrane protein classifications, this protein is MOST likely categorized as:

Type III membrane protein.
Type VI membrane protein. (correct)
Type II membrane protein.
Type I membrane protein.

A mutation in a cell line prevents the addition of GPI anchors to proteins. Which cellular process would be MOST directly affected by this mutation?

Anchoring of proteins to the extracellular leaflet of the plasma membrane. (C) Signup and view all the answers

The transmembrane domain of glycophorin A, an erythrocyte membrane protein, spans approximately 19 amino acids. Given the properties of amino acids within a lipid bilayer, which amino acid composition would MOST likely be found in this region?

A high proportion of charged residues like glutamate and arginine. (D) Signup and view all the answers

Hydropathy plots are commonly used to predict transmembrane domains in proteins. A hydropathy plot of a novel protein shows a region with a sustained, positive hydropathy index spanning 21 amino acids. What conclusion can be drawn?

The protein contains a transmembrane domain of approximately 21 amino acids. (C) Signup and view all the answers

In the context of membrane protein structure, which statement BEST describes the typical distribution of amino acid residues at the water-lipid interface?

Polar, uncharged residues are excluded from this region to maintain membrane integrity. (C) Signup and view all the answers

A researcher analyzing the structure of a glucose transporter (GLUT1) observes that the channel region is lined with specific amino acids that form hydrogen bonds with glucose. Which amino acid side chains are MOST likely involved in this interaction?

Amino acids with hydroxyl groups, such as serine, threonine, and asparagine. (C) Signup and view all the answers

E. coli lactose permease undergoes a conformational change due to protonation of a Glu325-Arg302 salt bridge, driven by a transmembrane proton gradient. If the glutamate residue is mutated to alanine, what would be the MOST likely consequence?

Inhibition of lactose transport due to disruption of the salt bridge and impaired conformational change. (B) Signup and view all the answers

The calcium pump of sarcoplasmic reticulum (SERCA) is phosphorylated at Asp351, which is thought to cause a conformational change affecting calcium binding affinity. If a non-hydrolyzable analog of ATP is used in an experiment with SERCA, what would be the expected outcome?

SERCA will undergo the conformational change, but calcium release will be accelerated. (C) Signup and view all the answers

Human MDR1, an ABC transporter, mediates resistance to chemotherapeutic drugs like adriamycin and vinblastine. Overexpression of MDR1 in tumor cells would MOST directly result in:

Decreased drug interaction with target proteins. (C) Signup and view all the answers

The most common mutation in cystic fibrosis is the deletion of phenylalanine at position 508 (ΔF508) in the CFTR protein. This mutation impairs CFTR's ability to:

Undergo glycosylation in the endoplasmic reticulum. (D) Signup and view all the answers

Aquaporins such as AQP-1 facilitate rapid water transport across cell membranes while preventing the passage of ions. Which structural feature BEST explains this selectivity?

A conserved Asn-Pro-Ala (NPA) motif that orients water molecules and disrupts proton flow. (D) Signup and view all the answers

Potassium channels maintain a high concentration gradient of K⁺ by selectively allowing K⁺ to pass while excluding smaller ions like Na⁺. What is the PRIMARY mechanism for this selectivity?

Specific interactions between K⁺ ions and carbonyl oxygens lining the selectivity filter. (C) Signup and view all the answers

Valinomycin is an ionophore that selectively binds potassium ions and disrupts ion gradients across cell membranes. Its mechanism of action relies on:

Selectively binding K⁺ via carbonyl oxygen atoms and shielding it with valine-like side chains for membrane passage. (B) Signup and view all the answers

Which of the following scenarios would be MOST directly affected by a mutation that prevents the palmitoylation of a peripheral membrane protein?

The protein's proper localization and association with the plasma membrane. (C) Signup and view all the answers

A novel drug targets GSK3, preventing its phosphorylation by PKB. What would be the expected cellular outcome from this drug?

Increased PIP2 production. (B) Signup and view all the answers

You discover a new integral membrane protein with alternating stretches of polar and nonpolar amino acids. Secondary structure analysis reveals a repeating unit where every other amino acid extends outward. This protein is PRIMARILY composed of:

Beta-Barrel. (C) Signup and view all the answers

A research team is studying a membrane-bound enzyme involved in lipid metabolism. They discover that the enzyme's activity is significantly reduced when treated with a protease that does not disrupt the cell membrane. Which of the following conclusions is MOST plausible?

The enzyme is likely a peripheral membrane protein. (C) Signup and view all the answers

A cell line is engineered to express a modified version of bacteriorhodopsin with a mutation in a key residue involved in proton transport. Spectroscopic analysis reveals that the mutated protein still undergoes light-induced conformational changes, but proton pumping activity is abolished. This suggests that:

The light-induced conformational change is sufficient for proton transport. (C) Signup and view all the answers

The rapid synthesis of glycogen from glucose indicates the activation of glycogen synthase (GS). What is the relationship between insulin signalling through PI-3K and GSK3 activity in this process?

PI-3K activates GSK3, which then phosphorylates and activates GS. (C) Signup and view all the answers

Consider a cell with a mutation rendering it unable to glycosylate proteins. Which class of membrane proteins would be MOST directly affected?

Cytosolic Proteins. (A) Signup and view all the answers

A researcher discovers a new bacterial toxin that disrupts membrane integrity by forming large pores. Analysis reveals the toxin consists of multiple identical subunits that assemble in the membrane. This toxin is likely a:

ẞ-barrel Protein. (C) Signup and view all the answers

Which of the following is the PRIMARY reason why obtaining high-resolution structural information for membrane-bound proteins is generally more challenging than for soluble proteins?

Membrane proteins are typically more stable than soluble proteins, making crystallization difficult. (C) Signup and view all the answers

Explain how the intrinsic properties of amino acids, specifically their hydropathy indices, dictate the positioning of transmembrane proteins within the lipid bilayer, and how this relates to the function of proteins like bacteriorhodopsin.

Amino acids with positive hydropathy indices are hydrophobic and will associate with the lipid core, while those with negative indices are hydrophilic and will interact with the aqueous environment. Bacteriorhodopsin's transmembrane helices are rich in hydrophobic residues, ensuring its stable integration within the membrane. Signup and view all the answers

Describe the structural and functional implications of having multiple transmembrane helices in integral membrane proteins, referencing specific examples like the glucose transporter GLUT1.

Multiple transmembrane helices allow for the formation of channels or pores, enabling selective transport of molecules across the membrane. In GLUT1, these helices create a hydrophilic pathway for glucose, alternating between inward-facing and outward-facing conformations. Signup and view all the answers

Explain the role of lipid anchors in membrane protein localization and function, detailing the chemical nature of these anchors and their targeting specificity.

Lipid anchors, such as myristoylation or palmitoylation, covalently attach proteins to the lipid bilayer, restricting their movement to the membrane. Different lipid modifications target proteins to specific membrane subdomains, influencing protein-protein interactions and signaling. Signup and view all the answers

Discuss the mechanisms by which reversible phosphorylation modulates the activity of membrane-bound proteins, using the insulin signaling pathway as a prime example.

Reversible phosphorylation, catalyzed by kinases and phosphatases modifies protein conformation and interaction. In insulin signaling, phosphorylation of IRS-1 activates PI-3K, initiating a cascade that ultimately leads to increased glucose uptake by GLUT4 translocation. Signup and view all the answers

Describe the structural basis for the specificity of potassium channels, focusing on the role of the selectivity filter and the energetic considerations involved in ion permeation.

Potassium channels utilize a selectivity filter composed of carbonyl oxygen atoms that precisely coordinate K+ ions, mimicking their hydration shell. The energy gained from this coordination compensates for the energy required to strip the ion of its water molecules, allowing selective passage of K+ over smaller ions like Na+. Signup and view all the answers

Detail the structural differences between Type I and Type II transmembrane proteins and how these differences influence their orientation and function within the cell membrane.

Type I transmembrane proteins have their N-terminus outside the cell and a stop-transfer anchor sequence. Type II proteins have their C-terminus outside the cell and a signal-anchor sequence, which dictates orientation with the N-terminus facing the cytoplasm. Signup and view all the answers

Explain how mutations in the CFTR protein, specifically the deletion of phenylalanine at position 508 (ΔF508), lead to cystic fibrosis, and what cellular mechanisms are disrupted by this mutation.

The ΔF508 mutation causes misfolding of the CFTR protein, leading to its retention in the endoplasmic reticulum and subsequent degradation. This prevents the protein from reaching the plasma membrane, resulting in impaired chloride ion transport and the characteristic symptoms of cystic fibrosis. Signup and view all the answers

Discuss the function of ABC transporters in the context of multidrug resistance (MDR) in cancer cells, highlighting the specific mechanisms by which these transporters reduce the efficacy of chemotherapeutic agents.

ABC transporters, such as MDR1 (P-glycoprotein), actively pump chemotherapeutic drugs out of cancer cells, reducing their intracellular concentration and therapeutic efficacy. This efflux mechanism contributes to the development of multidrug resistance, limiting treatment options. Signup and view all the answers

Describe the role of aquaporins in maintaining water balance in cells and tissues, detailing the structural features that enable rapid and selective water transport while preventing proton leakage.

Aquaporins form water-selective channels in cell membranes, facilitating rapid water transport along osmotic gradients. The narrow pore and positive charges in the channel prevent the passage of protons, maintaining electrochemical gradients crucial for cellular function. Signup and view all the answers

Articulate the dynamic equilibrium that valinomycin disrupts in cells, and explain why this disruption is lethal.

Valinomycin mediates potassium ion transport across cell membranes down the electrochemical gradient, disrupting the delicate balance of potassium concentration on either side of the membrane, leading to cell death by equilibrating the ionic concentration. Signup and view all the answers

Explain the function of signal-anchor sequences in membrane protein insertion and orientation, contrasting their mechanism with that of stop-transfer anchor sequences.

Signal-anchor sequences initiate insertion into the ER membrane and also determine the protein's orientation, with the N-terminus facing either the cytoplasm or the ER lumen. Stop-transfer sequences halt translocation, anchoring the protein in the membrane with the C-terminus remaining in the cytoplasm. Signup and view all the answers

Describe the mechanism by which the E. coli lactose permease utilizes a proton gradient to transport lactose across the bacterial membrane, and explain the role of the Glu325-Arg302 salt bridge in this process.

The lactose permease uses a proton gradient to drive lactose symport. Protonation changes at Glu325 and Arg302 alter the protein's conformation, facilitating lactose binding and translocation across the membrane, driven coupled to proton movement. Signup and view all the answers

Delineate the conformational changes that occur in the sarcoplasmic reticulum Ca2+-ATPase (SERCA pump) during the transport cycle, and how these changes affect the affinity for calcium ions and ATP.

SERCA pump undergoes phosphorylation of Asp351 causing conformational change that altering the binding affinity for calcium and enabling its transport into the sarcoplasmic reticulum. The cycle involves transitions between E1 (high Ca2+ affinity) and E2 (low Ca2+ affinity) conformations. Signup and view all the answers

Describe the structure and function of β-barrel membrane proteins, including the characteristics that allows seven hydrophobic amino acids to span the membrane.

β-barrel membrane proteins form a cylindrical structure with β-strands arranged in an antiparallel manner. The extended conformation of β-sheets allows just 7 hydrophobic residues to traverse the membrane. Signup and view all the answers

Explain the role of histidine residues located within the water-filled pore of aquaporins in preventing proton transport, clarifying how these residues contribute to the protein's selectivity.

Histidine residues create a steric and electrostatic barrier, preventing the formation of a continuous chain of hydrogen bonded water molecules. These residues prevent proton hopping/Grotthuss mechanism. Signup and view all the answers

Describe the role of lysine residues in the function and structure of positively charged membrane proteins, explain how interactions could stabilize structure.

Lysine residues are positively charged amino acids that can form electrostatic interactions with negatively charged lipid headgroups, and stabilize the lipid bilayer, contributing to membrane protein structure and function. Signup and view all the answers

How do the structural properties of sterols and lipid head groups in membranes influence the function and dynamics of membrane-bound proteins?

Membrane rigidity is modulated by sterols; influencing lipid packing & modulating membrane fluidity. The dynamics and function of membrane-bound proteins are also affected. Signup and view all the answers

Describe in detail how single-particle cryo-electron microscopy (cryo-EM) has revolutionized the structural determination of membrane proteins?

By enabling visualization of proteins in near-native conditions, cryo-EM minimizes artifacts induced during crystallization. Structural determination accuracy with enhanced resolution is now possible. Signup and view all the answers

Outline the molecular strategies that some viruses exploit to manipulate host-cell membrane proteins for their advantage.

Viruses manipulate host cell membrane proteins by altering protein trafficking and signaling pathways to recruit cellular factors for efficient replication and immune evasion. Viral factors compete with cellular ligands to interact with cellular receptors, and dysregulation of host membrane dynamics. Signup and view all the answers

Compare and contrast the functions of flippases, floppases, and scramblases in maintaining lipid asymmetry in the plasma membrane, and detail their roles in cellular processes.

Flippases mediate the inward movement of lipids from the outer to the inner leaflet using ATP. Floppases ATP-dependently move lipids from inner to outer membranes. Scramblases, influenced by calcium, non-selectively equilibrate lipids across the lipid bilayer. Signup and view all the answers

Explain how post-translational modifications such as glycosylation affect membrane protein structure, function, and immunogenicity.

Glycosylation contributes to correct protein folding and stability as well as modulating protein-protein interactions. Furthermore, glycosylation can enhance the immunogenicity of proteins and alter protein trafficking. Signup and view all the answers

Discuss the role of membrane microdomains (lipid rafts) in organizing membrane proteins and influencing cellular signaling pathways.

Lipid rafts facilitate the organization of specific proteins into functional clusters by acting as platforms where particular membrane components can congregate. Because of this action, they can enhance signaling efficiency and specificity by bringing signaling molecules closer togther. Signup and view all the answers

Outline the methodologies for studying lateral diffusion and mobility of membrane proteins within cellular membranes.

Lateral diffusion is studied using FRAP and single particle tracking techniques, while protein mobility requires computation and model analysis in the same way as other physical measurements. Signup and view all the answers

Membrane remodeling and curvature are critical aspects of cellular processes; how are proteins that are binding curvature affected by function?

Proteins can bind to curved membranes because of electrostatic interactions, hydrophobic interactions, and protein scaffolding which support membrane fission, vesicle formation, and even cellular migration. Signup and view all the answers

Describe the methods available for assessing and modulating interactions between peripheral membrane proteins and the lipid bilayer.

Interactions are assessed using surface plasmon resonance and quartz crystal microbalance (QCM-D) to measure binding kinetics. Protein and lipid modifications allow for these interactions to be modulated. Signup and view all the answers

Flashcards

What are kinases?

Enzymes that catalyze the reversible phosphorylation of specific serine, threonine, and tyrosine residues within other proteins.

Role of IRS-1 in signaling pathways?

IRS-1 is phosphorylated by the insulin receptor and activates PI-3K by binding to its SH2 domain. PI-3K converts PIP2 to PIP3.

Role of GSK3 in Glycogen Synthatase pathways?

GSK3 inactivated by phosphorylation cannot convert glycogen synthase (GS) to its inactive form, so GS remains active.