Name: how membrane proteins span cell membranes
Uploaded: 2023-04-30T09:16:08.000Z
Duration: 1 min 25 s
Channel: JoVE

K12 Standards

Alabama Course of Study Science

9-12

Biology

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

9-12.B.1.4.a

Single-pass Transmembrane Proteins

Transmembrane proteins are embedded in the lipid bilayer and have domains on either side of the membrane in addition to their transmembrane domains. They constitute about 25% of the proteins coded in the human genome and have various roles, including transporters, enzymes, and receptors.
The transmembrane domain, the membrane-spanning region of the protein, contains non-polar amino acids that form hydrophobic sections. In contrast, the cytosolic and exoplasmic domains are often hydrophilic.
Depending on the number of times the polypeptide chain crosses the membrane, transmembrane proteins can be classified as either single-pass or multi-pass proteins.
A single-pass protein contains approximately 20 to 30 non-polar amino acid residues spanning the membrane. This pass is most often an alpha-helix positioned vertically or slanted in the membrane.
In an alpha helix, the carbonyl and amide groups in the peptide backbone form hydrogen bonds, while the non-polar side groups point outwards into the hydrophobic environment of the membrane.
Single-pass proteins may form homo- or hetero-oligomers through non-covalent interactions.

single-pass transmembrane proteins

Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane proteins contain the cytoplasmic, transmembrane, and exoplasmic domains. Proteins embedded only in the membrane, without having an exoplasmic or cytoplasmic domain, are not yet discovered.
Single-pass membrane proteins, like receptor tyrosine kinase, contain only one transmembrane &#945;-helix domain. In the majority of membrane proteins, the transmembrane domain is &#945;-helix containing around 20-30 non-polar amino acids. This characteristic amino acid sequence in the &#945;-helix of the transmembrane proteins is used to identify the potential transmembrane domains present in a protein using the hydropathy plot. The free energy required to transfer an amino acid from an aqueous to a lipid medium is used to generate the hydropathy plot. The average energy values of the polypeptide segments give information about potential transmembrane domains present in a protein. A hydropathy plot can help identify whether a particular protein is a single-pass or multi-pass membrane protein.
Transmembrane proteins play an essential role in a cell&#39;s interaction with the extracellular environment. Therefore, transmembrane proteins are the target for more than 50% of the available drugs and are of great pharmacological importance. A better knowledge of the structure and function of transmembrane proteins can help understand the pathogenesis of several diseases and the relevant drug discovery.

Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport ...

Education

JoVE Core

Cell Biology

Unit 1

Membrane Structure and Components

KEY TERMS AND CONCEPTS

how membrane proteins span cell membranes

Membrane proteins help cells communicate, send signals, stick to other cells, and move molecules across the membrane. Integral membrane proteins are tightly linked to the cell membrane and carry out these jobs.

Some integral membrane proteins sit only in one membrane layer. Fatty acid amide hydrolase is one example, and it is found on the cytoplasmic side of the membrane monolayer. Other integral membrane proteins are transmembrane proteins, which span across the membrane. These proteins have cytoplasmic, transmembrane, and exoplasmic domains.

Single-pass membrane proteins are a type of transmembrane protein with only one transmembrane alpha-helix. Receptor tyrosine kinase is one example. In most membrane proteins, this transmembrane segment is an alpha-helix with about 20 to 30 non-polar amino acids. Proteins embedded only in the membrane, without exoplasmic or cytoplasmic domains, have not yet been discovered.

Scientists use a hydropathy plot to look for likely transmembrane regions in a protein. This plot is based on the free energy needed to move amino acids from water into a lipid environment. Average energy values along a polypeptide chain can point to possible membrane-spanning segments. A hydropathy plot can also help show whether a protein is single-pass or multi-pass.

Transmembrane proteins are important for how cells interact with the outside environment. Because of this, they are targets for more than 50% of available drugs. Their structure and function are important in understanding disease and supporting drug discovery.

How Membrane Proteins Span Cell Membranes

how-membrane-proteins-span-cell-membranes

what are membranes?

Membrane Receptors and Cell Signals

The plasma membrane sets the outer boundary of a cell and helps control how the cell interacts with its environment. It lets some substances enter, keeps others out, and releases some materials in controlled amounts. The membrane also needs to stay flexible so cells such as red and white blood cells can change shape as they move through narrow capillaries. The membrane surface also carries markers that help cells recognize one another. This recognition is important during early development,...

membrane fluidity

How Cell Membranes Stay Flexible

Cell membranes stay flexible because of the fluid mosaic model. The plasma membrane is a mosaic of phospholipids, cholesterol, proteins, and carbohydrates. These parts are separate but loosely attached, so the membrane keeps a fluid character. The membrane is still fairly rigid, but it can flow and self-seal after a very fine needle passes through it. Phospholipid tails also affect membrane fluidity. Saturated fatty acids in phospholipids have straight tails because they are packed with...

fluid mosaic model

Fluid Mosaic Model of the Membrane

The fluid mosaic model explains the structure and function of the plasma membrane. Scientists first identified the plasma membrane in the 1890s, and by 1915 they had identified its main chemical parts: lipids and proteins. Early electron micrographs showed a railroad track pattern, which helped lead to the first widely accepted membrane model in 1935.

membrane lipids

Membrane Lipids in Cells and Tissues

Membrane lipids give biological membranes their structure and help set their properties. In mammalian cells, lipids make up about 50% of the membrane on average. The amount can be much lower in the inner mitochondrial membrane or much higher in the myelin sheath around nerve cells. Several phospholipids are common in mammalian membranes. These include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin. At physiological pH, phosphatidylserine carries a negative...

asymmetric lipid bilayer

Membrane Lipid Unevenness

Biological membranes have an uneven mix of lipids between the inner and outer layers. This membrane asymmetry gives each side a different chemical makeup and supports different cell functions. Evidence for this uneven layout came from treating an erythrocyte membrane with phospholipase. Phospholipase is an enzyme that breaks lipids into fatty acids and hydrophilic groups. It acted only on the outer layer, while the inner layer stayed intact. The treatment degraded about 80% of total membrane...

membrane asymmetry regulating transporters

membrane-asymmetry-regulating-transporters

Membrane Lipid Flipping and Transport

Membrane lipid flipping and transport help cells keep an uneven, or asymmetric, distribution of phospholipids across the membrane. This balance is controlled by flippase, floppase, and scramblase enzymes, which move lipids between the two membrane leaflets. Flippases move specific phospholipids from the outer leaflet to the inner leaflet. In eukaryotes, these enzymes are type-IV P-type ATPases, also called P4-ATPases. They are membrane pumps that use ATP and contain one transmembrane domain...

membrane carbohydrates

Membrane Sugars and Cell Identity

Membrane carbohydrates help give cells their surface identity and support plasma membrane function. The plasma membrane is a dynamic barrier made of lipids, proteins, and carbohydrates. These sugar chains have unique structural and chemical traits that help the membrane work properly for cell growth and survival. Membrane carbohydrates do not have a hydrophobic region, so they are found only on the outer surface of the cell. Sugar addition, or glycosylation, of proteins occurs in the lumens of...

membrane proteins

Facilitated Transport Across Cell Membranes

Facilitated transport uses membrane proteins to help materials cross the plasma membrane. These integral transmembrane proteins act as channels or carriers. They move selected substances through the membrane more easily than the lipid layer alone would allow. Channel proteins provide a hydrophilic, or water-friendly, path through the membrane. Their core forms a hydrated opening that lets solutes pass between the inside and outside fluids of the cell. This helps polar compounds avoid the...

lipids as anchors

Lipid Anchors in Membrane Proteins

Lipid anchors help attach proteins to the plasma membrane. In eukaryotic cells, the main lipid anchors are prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol, or GPI, groups. Prenyl and fatty acyl groups anchor proteins on the cytosolic side of the membrane. GPI anchors proteins on the extracellular side. Prenylated proteins often have a CaaX motif at the carboxy terminus. In this sequence, C means cysteine, a means any aliphatic amino acid, and X means any other amino acid...

Membrane proteins help cells communicate, send signals, stick to other cells, and move molecules across the membrane. Integral membrane proteins are tightly linked to the cell membrane and carry out these jobs. Some integral membrane proteins sit only in one membrane layer. Fatty acid amide hydrolase is one example, and it is found on the cytoplasmic side of the membrane monolayer. Other integral membrane proteins are transmembrane proteins, which span across the membrane. These proteins have...

multi-pass transmembrane proteins and &#946;-barrels

multi-pass-transmembrane-proteins-and-barrels

Membrane-Spanning Helices and β-Barrels

Membrane-spanning proteins can cross the cell membrane more than once. Their transmembrane chain usually folds into either an alpha-helix or a beta-strand. Alpha-helix multi-pass proteins are common, while beta-strand proteins are found mainly in gram-negative bacteria, mitochondria, and chloroplasts. Some multi-pass alpha-helix proteins are G-protein-linked receptors, or GPCRs, and bacteriorhodopsin. GPCRs have seven transmembrane alpha-helices. Each receptor also has its own extracellular...

detergent purification of membrane proteins

detergent-purification-of-membrane-proteins

How Detergents Solubilize Membrane Proteins

Detergents help solubilize membrane proteins so they can be purified from the lipid bilayer. Their hydrophobic region can replace membrane phospholipids and keep integral membrane proteins in solution. A detergent works well only when its monomers reach the critical micelle concentration, or CMC. At that point, the molecules assemble into micelles, which are small clusters of detergent. Above the CMC, free detergent monomers stay in equilibrium with the micelles. The CMC varies with the...

protein diffusion in the membrane

How Membrane Proteins Move Side to Side

Membrane proteins can move across the cell surface by lateral diffusion, and they can also rotate in place. Scientists confirmed lateral movement with a cell fusion experiment. Mouse and human cells were fused to make hybrid cells. The membrane proteins on the two cells were tagged with red and green fluorescent markers. At first, each color stayed on its own side of the fused cell. After 40 minutes, the colors mixed across the whole cell surface, showing that the proteins had moved laterally. <br...

membrane domains

Lipid Rafts and Sperm Membrane Regions

Membrane domains organize specific lipids and proteins in defined parts of a cell membrane. This arrangement supports cell signaling, adhesion, and other important cellular processes. These domains can vary in size, composition, function, and how long they last. Some membrane domains are built from proteins. The membrane can contain distinct protein groups that carry out a cell’s specific functions. A clear example is the plasma membrane of a human sperm cell, which has different proteins in...

mechanisms of membrane domain formation

How Cell Membranes Form Domains

Cell membranes form domains when lipids and proteins gather into distinct regions. These regions, or membrane domains, are shaped by different physical properties that help some molecules stay together while others move apart. Some domains form through protein-protein interactions. Others depend on specific lipids, such as sphingolipids and sterols. Large proteins, including bacteriorhodopsin, can also cluster and create visible membrane domains. Membrane proteins can be held in place by...

mechanisms of membrane-bending

How Proteins Shape Cell Membranes

Cell membranes can bend into many shapes because they are flexible and made of a fluid mosaic. That bending can be temporary, as in vesicles, or long-lasting, as in microvilli. Cells control the size, place, and time of membrane curvature. Membrane bending can start inside the membrane itself or from proteins attaching to it. Changes in lipid makeup can create curvature, and proteins can help by making the membrane asymmetric or by clustering certain lipids. The shape of integral proteins also...

key terms and concepts

Learn how transmembrane proteins span cell membranes, how hydropathy plots identify membrane domains, and why these proteins matter in cell signaling and drug targets.

How Membrane Proteins Span Cell Membranes | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

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9-12.B.1.1

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Transcription Elongation Factors

pre-mrna-processing-modification-of-pre-mrna-ends

Pre-mRNA Processing: Modification of pre-mRNA Ends

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Pre-mRNA Processing: RNA Splicing

Chromatin Structure and RNA Splicing

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Nuclear Export of mRNA

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Ribosomal RNA Synthesis

The Nucleolus

Additional Subnuclear Structures

Translation

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tRNA Activation

Initiation of Translation

Termination of Translation

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prokaryotic-transcriptional-activators-and-repressors

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Nonsense-mediated mRNA Decay

The Eukaryotic Promoter Region

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regulation-of-expression-occurs-at-multiple-steps

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cooperative-binding-of-transcription-regulators

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9-12.B.1.2

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9-12.B.1.2.a

How Membrane Proteins Span Cell Membranes

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