lecture 3- Membrane components Flashcards
1.What are the components of a cell membrane
- Phospholipids
Structure: Phospholipids have a hydrophilic (water-attracting) “head” and two hydrophobic (water-repelling) “tails.” They arrange themselves in a bilayer, with the heads facing outward toward the aqueous environment and the tails facing inward, away from water.
Function: The phospholipid bilayer forms the basic structure of the cell membrane, providing a barrier to most water-soluble substances. - Proteins
Types:
Integral Proteins: These proteins span the entire membrane and are embedded in the lipid bilayer. They can function as channels, transporters, or receptors.
Peripheral Proteins: These proteins are located on the inner or outer surface of the membrane and are not embedded in the lipid bilayer. They often play roles in signaling or maintaining the cell’s shape.
Function: Membrane proteins facilitate communication, transport, and enzymatic activities, and help maintain the structure of the membrane. - Carbohydrates
Location: Carbohydrates are often attached to proteins (glycoproteins) or lipids (glycolipids) on the extracellular surface of the membrane.
Function: They play a critical role in cell recognition, signaling, and adhesion. They also contribute to the formation of the glycocalyx, a protective layer on the cell surface. - Cholesterol
Structure: Cholesterol molecules are interspersed within the phospholipid bilayer.
Function: Cholesterol helps to stabilize the membrane’s fluidity, making it less permeable to very small water-soluble molecules that might otherwise pass freely through. It also prevents the fatty acid chains of phospholipids from packing too closely together, maintaining membrane flexibility. - Cytoskeleton
Components: The cytoskeleton consists of protein filaments and tubules, including microfilaments, intermediate filaments, and microtubules.
Function: While not a direct component of the membrane, the cytoskeleton provides structural support and helps maintain the shape of the cell. It is also involved in the transport of materials within the cell and in cell signaling.
Summary
The cell membrane is a complex structure composed of phospholipids, proteins, carbohydrates, cholesterol, and is supported by the cytoskeleton. This arrangement allows the cell membrane to perform essential functions such as protecting the cell, facilitating communication and transport, and maintaining the cell’s structural integrity. The dynamic nature of the cell membrane is crucial for its role in various cellular processes.
2.How do the properties of the components influence the properties of the membrane
The properties of the components of the cell membrane significantly influence the overall characteristics and functions of the membrane. Here’s how each component contributes to the properties of the membrane:
- Phospholipids
Fluidity: The amphipathic nature of phospholipids (having hydrophilic heads and hydrophobic tails) allows them to form a bilayer. This bilayer structure creates a fluid environment that is essential for the movement of proteins and lipids within the membrane.
Selective Permeability: The hydrophobic interior of the bilayer acts as a barrier to most polar and charged substances, allowing only small nonpolar molecules (e.g., oxygen, carbon dioxide) to pass freely. This selective permeability is crucial for maintaining the internal environment of the cell.
Flexibility: The fluidity of the membrane allows cells to change shape and enables processes like endocytosis and exocytosis. - Proteins
Functional Diversity: Integral proteins can form channels or transporters that facilitate the movement of ions and molecules across the membrane. This function is vital for nutrient uptake and waste removal.
Cell Communication: Membrane proteins act as receptors that bind to signaling molecules (e.g., hormones, neurotransmitters), triggering cellular responses. This capability is crucial for communication between cells and their environment.
Structural Support: Peripheral proteins and cytoskeletal attachments provide structural integrity and help maintain the shape of the cell, influencing its mechanical properties. - Carbohydrates
Cell Recognition: Carbohydrates attached to proteins and lipids (glycoproteins and glycolipids) play a key role in cell-cell recognition and signaling. This is vital for immune responses, tissue formation, and cellular interactions.
Protection: The glycocalyx, formed by carbohydrate-rich molecules on the extracellular surface, protects the cell from mechanical damage and helps with cell adhesion. - Cholesterol
Membrane Fluidity Regulation: Cholesterol helps to maintain membrane fluidity by preventing the fatty acid chains of phospholipids from packing too closely together. This stabilization allows the membrane to remain fluid at various temperatures.
Barrier to Small Molecules: By interspersing within the phospholipid bilayer, cholesterol reduces permeability to small polar molecules, contributing to the selective permeability of the membrane.
Formation of Lipid Rafts: Cholesterol can lead to the formation of microdomains called lipid rafts, which concentrate specific proteins and lipids, facilitating signaling and membrane trafficking. - Cytoskeleton
Structural Support: The cytoskeleton provides mechanical support and helps maintain the shape of the cell. It also anchors certain proteins in the membrane, influencing their localization and function.
Dynamic Movement: The interaction between the cytoskeleton and membrane components allows for dynamic changes in cell shape, facilitating processes like cell division, migration, and intracellular transport.
Summary
The interplay between these components gives the cell membrane its unique properties: fluidity, selective permeability, structural integrity, and dynamic responsiveness. These characteristics are essential for the cell’s ability to communicate with its environment, transport materials, maintain homeostasis, and adapt to changes. The specific composition and arrangement of these components ultimately determine how the membrane functions in various cellular processes.
Differences between cell types and organelles
Protein-membrane association- 8 mechanisms for insertion
The insertion of proteins and other molecules into the phospholipid bilayer of cell membranes is a complex process that can occur through several mechanisms. Here are eight mechanisms that facilitate the insertion of proteins and other components into the phospholipid bilayer:
- Co-Translational Insertion
Mechanism: As polypeptides are synthesized by ribosomes, they can be inserted into the membrane during translation. This occurs primarily for integral membrane proteins that have a hydrophobic signal sequence recognized by the signal recognition particle (SRP).
Process: The SRP binds the signal sequence and directs the ribosome to the endoplasmic reticulum (ER) membrane, where the protein is inserted into the lipid bilayer. - Post-Translational Insertion
Mechanism: Some proteins are fully synthesized before they are inserted into the membrane. This is common in mitochondria and plastids.
Process: Chaperone proteins assist in the proper folding of the protein and help it cross the membrane into the organelle, where it is inserted into the lipid bilayer. - Transmembrane Domain Insertion
Mechanism: Proteins with transmembrane domains contain hydrophobic regions that can span the lipid bilayer.
Process: These regions typically consist of alpha-helices or beta-barrels, which facilitate insertion by interacting favorably with the hydrophobic interior of the membrane. - Lipid Anchoring
Mechanism: Some proteins are anchored to the membrane through covalent attachment to lipid molecules (e.g., glycosylphosphatidylinositol (GPI) anchors).
Process: The lipid anchor embeds itself in the membrane, effectively tethering the protein to the membrane surface without the protein spanning the bilayer. - Membrane Fusion
Mechanism: Membrane fusion is a process where two lipid bilayers merge, allowing proteins from one membrane to integrate into another.
Process: This can occur during processes like vesicle trafficking (e.g., exocytosis or endocytosis), where vesicles fuse with the plasma membrane, inserting their contents (including proteins) into the membrane. - Lipid Raft Insertion
Mechanism: Lipid rafts are microdomains within the membrane that are rich in cholesterol and sphingolipids.
Process: Certain proteins preferentially associate with lipid rafts, facilitating their insertion into these specialized regions of the membrane, which can influence signaling and membrane trafficking. - Insertion via Membrane Transport Proteins
Mechanism: Some proteins are inserted into the membrane through the action of specialized transport proteins.
Process: For instance, bacterial membrane proteins can be inserted into the inner membrane through the Sec or Tat pathways, where chaperones help guide the proteins to the membrane. - Self-Insertion of Amphipathic Helices
Mechanism: Some proteins contain amphipathic helices that can insert into the membrane spontaneously.
Process: These helices can insert themselves into the lipid bilayer due to their dual affinity for both the hydrophobic core and the aqueous environment, often leading to the formation of pores or channels.
Summary
These mechanisms ensure that proteins and other molecules are properly inserted into the phospholipid bilayer, contributing to the structural integrity and functionality of the cell membrane. Each mechanism is critical for maintaining cellular processes such as signaling, transport, and interaction with the environment.
Integral membrane proteins are a type of membrane protein that are permanently attached to the cell membrane. They span the entire membrane, interacting with both the interior and exterior environments of the cell. These proteins have one or more regions embedded within the hydrophobic core of the lipid bilayer, often with hydrophilic regions exposed on both sides of the membrane.
There are two main types of integral membrane proteins:
- Transmembrane proteins: These span the membrane fully and usually have multiple membrane-spanning regions. They are involved in a variety of functions, including acting as channels, transporters, or receptors.
Single-pass transmembrane proteins: These have one alpha-helix segment passing through the membrane.
Multi-pass transmembrane proteins: These have multiple alpha-helical or beta-barrel segments that pass through the membrane.
- Monotopic integral proteins: These are embedded in only one side of the membrane and do not span the entire bilayer.
Key Functions:
Transport: They help move molecules and ions across the cell membrane.
Signal transduction: Many integral proteins act as receptors, receiving external signals and relaying them into the cell.
Cell adhesion: Some integral proteins help anchor cells to each other or to the extracellular matrix.
Enzymatic activity: Certain integral proteins have enzymatic functions, catalyzing reactions at the membrane.
Due to their amphipathic nature (having both hydrophobic and hydrophilic regions), they play critical roles in maintaining cellular integrity and enabling communication between the cell and its external environment. Their extraction and study often require the use of detergents, as they are difficult to solubilize without disrupting the lipid bilayer
Mechanisms of membrane insertion
1)Single pass proteins: alpha helix e.g. cell-cell junctions
2)Multipassproteins: Three (or more) distinct hydrophobic alpha helices. May forms multi-subunit channels e.g. Nicotinic Acetyl choline Receptors.
3)Channel: more complex because it has charged or polar groups facing inwards and vice versa on outside. e.g. porins in the GI Tract.
4)Not membrane spanning but embedded in the membrane: Protein is considered to be amphipathic. e.g. Adenylate cyclase.
5)Lipid anchored: Long chain fatty acid tethers protein to the membrane through Van der Waals forces between phospholipid tails and the fatty acid chain. e.g. Protein Kinase C
6)Glycolipid anchored: Fatty acid part enables tethering to the membrane but the carbohydrate part acts as a flexible linker enabling proteins to be near but not immediately next to the membrane. e.g. proteases
7)Adapter proteins: Use a transmembrane protein as an adapter to associate with the Inner leaflet of the membrane. e.g. enzyme linked receptors
8)Accessory proteins: Similar to adapter proteins but extracellular, enables extracellular matrix proteins to provide additional mechanical strength
Lipid anchors
Rely on interactions between fatty acid chain and phospholipid tails.
Raft formation ensures proximity to transmembrane proteins
Inserting proteins into membranes
➢Polypeptide chain needs to form a cylindrical structure, allowing charged/polar amino acids to be hidden from the hydrophobic middle of the bilayer.
➢Uncharged/non-polar amino acids on the outside of the cylinder enable interaction with fatty acid tails.
Multiple transmembrane regions
Polar or charged amino acids link transmembrane sections, which interact with aqueous environment.
Multiple transmembrane regions refer to segments of a protein that span the phospholipid bilayer of a cell membrane more than once. Proteins with multiple transmembrane domains are typically integral membrane proteins, meaning they are embedded within the lipid bilayer. Here’s a detailed look at the characteristics and significance of proteins with multiple transmembrane regions:
Structure of Proteins with Multiple Transmembrane Regions
- Transmembrane Domains:
Each transmembrane region typically consists of hydrophobic amino acids that allow the segment to interact favorably with the lipid bilayer.
These regions can form alpha-helices or beta-barrels:
Alpha-Helices: Many transmembrane proteins consist of several alpha-helical segments that traverse the membrane. Each helix usually contains around 20-25 hydrophobic amino acids.
Beta-Barrels: Some proteins, especially those in bacteria and mitochondria, can form beta-barrel structures composed of beta strands that fold into a barrel shape, allowing them to span the membrane.
- Orientation:
The orientation of the protein in the membrane is important. Typically, the N-terminus (amino terminus) is oriented toward the extracellular space, while the C-terminus (carboxyl terminus) is oriented toward the cytoplasm (or vice versa, depending on the protein).
- Loops:
Regions between the transmembrane segments are often hydrophilic and extend into the cytoplasm or extracellular space. These loops can serve important functions, such as being sites for post-translational modifications or acting as binding sites for ligands or other proteins.
Functions of Proteins with Multiple Transmembrane Regions
- Receptors:
Many receptors that bind hormones or neurotransmitters have multiple transmembrane regions. These proteins can initiate signaling cascades within the cell upon binding their ligands.
- Transport Proteins:
Proteins like channels and transporters often contain multiple transmembrane domains that create pathways for ions or molecules to cross the membrane. For example:
Ion Channels: Proteins like voltage-gated sodium channels have multiple transmembrane segments that open in response to changes in membrane potential, allowing ions to flow through.
Transporters: Proteins that facilitate the movement of substances across the membrane, such as glucose transporters, also have multiple transmembrane regions.
- Enzymes:
Some membrane-bound enzymes have multiple transmembrane regions that allow them to interact with substrates in the lipid bilayer or the surrounding environment, facilitating various metabolic processes.
- Cell Adhesion Molecules:
Proteins involved in cell-cell adhesion, like integrins, often have multiple transmembrane regions that interact with the extracellular matrix and other cells, playing a crucial role in tissue formation and immune response.
Examples of Proteins with Multiple Transmembrane Regions
- G Protein-Coupled Receptors (GPCRs):
These receptors typically have seven transmembrane domains and are involved in various signaling pathways.
- Ion Channels:
Examples include sodium, potassium, and calcium channels, which usually have multiple transmembrane segments forming a pore for ion conduction.
- Transporters:
GLUT (Glucose Transporter) family members often have multiple transmembrane domains facilitating glucose transport into cells.
- Aquaporins:
These proteins, which facilitate water transport, typically contain six transmembrane regions that form a channel for water molecules.
Summary
Proteins with multiple transmembrane regions are crucial for many cellular processes, including signaling, transport, and adhesion. Their unique structural features allow them to interact with both the hydrophobic interior of the lipid bilayer and the aqueous environments on either side, making them vital components of cell membranes. Understanding these proteins is essential for elucidating how cells communicate and interact with their surroundings.
Formation of large functional proteins within membranes
The formation of large functional proteins within membranes is a complex process involving several stages, including synthesis, insertion, folding, and assembly. Here’s an overview of how these proteins are formed and how they achieve their functional roles within cell membranes:
- Synthesis
Translation: Large proteins, including those that will reside in membranes, are synthesized by ribosomes in the cytoplasm. The genetic code from mRNA is translated into a polypeptide chain.
Signal Sequences: Many membrane proteins begin with a signal sequence at their N-terminus, which directs the ribosome to the endoplasmic reticulum (ER) for further processing. - Co-Translational Insertion
Rough Endoplasmic Reticulum (RER): For many integral membrane proteins, the insertion into the membrane occurs co-translationally. As the ribosome synthesizes the protein, it is targeted to the ER membrane.
Signal Recognition Particle (SRP): The signal sequence is recognized by the SRP, which halts translation momentarily and directs the ribosome to the ER membrane. The SRP binds to its receptor on the ER, facilitating the docking of the ribosome to a translocon.
Translocon: This protein complex allows the growing polypeptide chain to enter the membrane. The signal sequence is cleaved off, and the remaining protein segments are inserted into the lipid bilayer. - Folding and Post-Translational Modifications
Chaperone Proteins: Once inserted into the membrane, proteins may require the assistance of chaperone proteins to ensure proper folding. Chaperones prevent misfolding and aggregation, helping the protein achieve its native structure.
Post-Translational Modifications: Many membrane proteins undergo modifications such as glycosylation (addition of sugar molecules) or phosphorylation (addition of phosphate groups). These modifications can affect protein stability, localization, and function. - Assembly into Larger Complexes
Multimerization: Some membrane proteins function as part of larger complexes. They may associate with other proteins to form dimers, trimers, or larger oligomeric structures. This assembly can occur in the ER, Golgi apparatus, or at the plasma membrane.
Protein Interactions: Protein-protein interactions are often mediated by specific domains within the proteins that recognize and bind to each other. For example, transmembrane domains and cytoplasmic loops may facilitate these interactions. - Transport to the Membrane
Vesicular Transport: After synthesis and folding, proteins are packaged into transport vesicles that bud off from the ER and are sent to the Golgi apparatus for further processing and sorting.
Golgi Apparatus: The Golgi modifies, sorts, and packages proteins for delivery to their final destinations, including the plasma membrane or other organelles. - Insertion into the Membrane
Exocytosis: Membrane proteins destined for the plasma membrane are delivered via vesicles that fuse with the membrane. This process is known as exocytosis.
Orientation: Integral membrane proteins are inserted into the membrane in a specific orientation, with the N-terminus usually facing the extracellular space and the C-terminus in the cytoplasm. - Functional Integration
Functional Domains: Large membrane proteins often contain multiple functional domains, each contributing to specific roles such as signaling, transport, or structural support.
Role in Cellular Processes: These proteins can act as receptors, channels, transporters, or enzymes, playing critical roles in cell communication, nutrient uptake, ion transport, and maintaining cellular homeostasis. - Regulation and Turnover
Dynamic Regulation: The activity and localization of membrane proteins can be regulated by various factors, including ligand binding, phosphorylation, or interactions with other cellular components.
Endocytosis and Recycling: Membrane proteins can also be internalized via endocytosis for recycling or degradation, allowing for dynamic regulation of membrane composition and function.
Summary
The formation of large functional proteins within membranes is a multifaceted process involving synthesis, co-translational insertion, folding, assembly, and transport. These proteins play crucial roles in maintaining cellular functions and facilitating communication between the cell and its environment. Understanding these processes is fundamental to cell biology and has implications in fields such as pharmacology and biotechnology.
Filters
Charges and polarity in the centre of the pore of channel make it selective for its ligand- this is what gives the pores selectivity for its specific ligands
1.What structures do you know of that represent proteins in the membrane?
2.What are the functions of these?
- Structures of Membrane Proteins
a. Integral Membrane Proteins
Description: These proteins span the lipid bilayer, often with one or more transmembrane domains.
Types:
Single-pass: Cross the membrane once.
Multi-pass: Cross the membrane multiple times, forming several transmembrane domains.
Examples: G protein-coupled receptors (GPCRs), ion channels, and transporters.
b. Peripheral Membrane Proteins
Description: These proteins are not embedded in the lipid bilayer but are loosely associated with the membrane’s surface, often through interactions with integral proteins or the polar head groups of lipids.
Examples: Spectrin, which supports the cytoskeleton, and some signaling proteins.
c. Lipid-anchored Proteins
Description: These proteins are covalently attached to lipid molecules, which embed them in the membrane. They do not span the bilayer.
Examples: GPI-anchored proteins that are involved in cell signaling.
d. Beta-Barrel Proteins
Description: These are a type of integral protein that forms a barrel-like structure made of beta sheets. They are typically found in the outer membranes of bacteria, mitochondria, and chloroplasts.
Examples: Porins, which allow the passage of small molecules and ions.
- Functions of Membrane Proteins
a. Transport
Function: Integral proteins, such as channels and transporters, facilitate the movement of ions, small molecules, and nutrients across the membrane.
Examples:
Ion Channels: Allow the passive transport of ions (e.g., sodium, potassium).
Transporters: Mediate the active transport of substances against their concentration gradient (e.g., glucose transporters).
b. Receptors
Function: Membrane proteins act as receptors that bind specific ligands (e.g., hormones, neurotransmitters), initiating signal transduction pathways that result in cellular responses.
Examples:
G Protein-Coupled Receptors (GPCRs): Activate intracellular signaling
cascades in response to external signals.
Tyrosine Kinase Receptors: Involved in cell growth and differentiation signaling.
c. Enzymatic Activity
Function: Some membrane proteins have enzymatic functions, catalyzing biochemical reactions at the membrane surface.
Examples:
ATP Synthase: Located in the inner mitochondrial membrane, it synthesizes ATP during oxidative phosphorylation.
Phospholipases: Involved in the metabolism of phospholipids, which can influence membrane composition and signaling.
d. Cell Adhesion
Function: Proteins involved in cell-cell or cell-matrix adhesion help maintain tissue structure and facilitate communication between cells.
Examples:
Cadherins: Mediate cell-cell adhesion in tissues.
Integrins: Connect cells to the extracellular matrix and play a role in signaling.
e. Structural Support
Function: Peripheral proteins and cytoskeletal components provide structural integrity and shape to the cell membrane.
Examples:
Spectrin: Forms a cytoskeletal meshwork beneath the plasma membrane, maintaining cell shape in red blood cells.
Actin Filaments: Involved in various cell shape changes and motility.
f. Signal Transduction
Function: Membrane proteins can act as components of signaling pathways, transmitting information from the extracellular environment to the intracellular environment.
Examples:
Receptor Tyrosine Kinases: Initiate signaling cascades that regulate cell division and survival.
GPCRs: Activate G proteins, which then influence various intracellular signaling pathways.
g. Recognition and Communication
Function: Glycoproteins and glycolipids on the extracellular surface of the membrane are involved in cell recognition and communication.
Examples:
Cell Surface Markers: Play roles in immune responses and tissue recognition.
Antigen Presenting Proteins: Important for immune cell recognition and activation.
Summary
Membrane proteins exhibit diverse structures, including integral, peripheral, and lipid-anchored forms. Their functions encompass transport, signaling, enzymatic activity, adhesion, structural support, and communication, making them essential for maintaining cellular integrity and facilitating interactions with the environment. Understanding these proteins is crucial for comprehending cellular processes and the overall function of living organisms.
Glycolipids
*Made of a diglyceride attached to a carbohydrate
*Diglyceride acts as the anchor
*Immune recognition
*Involved in determination of self
Glycoproteins
Usually part of complex, multi subunit receptors
Carbohydrate chain acts to restrict movement or scaffold structures
E.g. Proteoglycans: Essential for interaction with the extracellular matrix
Functions of glyco-additions
*Support interactions of a receptor with its ligand.
*Can act as part of ligand recognition site
