Name: lipid anchors in membrane proteins
Uploaded: 2023-04-30T09:16:02.000Z
Duration: 1 min 32 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

Lipids as Anchors

The three most common types of lipid anchors are prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI anchors.
The prenyl groups are the 15 carbon farnesyl and the 20 carbon geranylgeranyl groups. They bond to cysteine residues at or near the carboxy terminus of proteins.&#160;&#160;
Saturated 14 carbon myristic acid and the 16 carbon palmitic acid are the most common fatty acyl anchors linked to proteins.
The addition of myristic acid, or myristoylation, happens at a protein&#39;s N-terminal glycine residue. Palmitoylation of the proteins can occur at the N- or C- terminal cysteine residue.
Prenylated, myristoylated, and palmitoylated proteins play an essential role in intracellular signaling pathways and protein-protein interactions.
GPI anchors attach to extracellular proteins and contain a core structure of phosphatidylinositol, glucosamine, three mannoses, and phosphoethanolamine.
The phosphoethanolamine bonds to the C-terminal amino acid of the target protein, and the phospholipid inserts itself into the outer layer of the membrane.
This allows GPI anchored proteins to participate in extracellular functions such as cell-cell communication and cell adhesion.

lipids as anchors

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are &#8211; prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the CaaX motif or CaaX box where &#34;C&#34;&#160;stands for cysteine, &#34;a&#34;&#160;stands for any aliphatic amino acid, and &#34;X&#34;&#160;stands for any other amino acid residue. The amino acid present at the &#34;X&#34;&#160;position determines whether the linkage to the protein will be the farnesyl or the geranylgeranyl linkage.&#160; If the &#34;X&#34;&#160;is alanine, serine, methionine, cysteine, or glutamine, then farnesyl transferase recognizes the CaaX motif and links farnesyl to the protein. On the other hand, if the &#34;X&#39;&#34;&#160;is glutamic acid or leucine, then geranyl transferase type I identifies the CaaX motif and attaches geranylgeranyl to it. After prenylation, the tripeptide aaX is removed by specific proteases, and a methyltransferase methylates the resultant negatively charged cysteine residue. Methylation removes the negative charge present on the cysteine and makes it hydrophobic.
Sometimes more than one lipid anchor is used to link protein to the membrane. For example, cytoplasmic tyrosine kinase is anchored to the membrane with the help of myristic and palmitic acid. However, GPI anchored proteins usually do not need another anchor for stabilization. One end of the GPI contains the two fatty acyl groups that can be inserted into the lipid bilayer. In contrast, on the other end, the phosphoethanolamine attaches to the target proteins involved in different cell functions.&#160;

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors ...

Education

JoVE Core

Cell Biology

Unit 1

Membrane Structure and Components

KEY TERMS AND CONCEPTS

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 residue. The amino acid at the X position helps decide the type of linkage. If X is alanine, serine, methionine, cysteine, or glutamine, farnesyl transferase attaches a farnesyl group. If X is glutamic acid or leucine, geranylgeranyl transferase type I attaches a geranylgeranyl group.

After prenylation, specific proteases remove the aaX tripeptide. Then a methyltransferase methylates the cysteine that remains. This step removes the negative charge on the cysteine and makes it more hydrophobic. The change helps the protein stay associated with the membrane.

Some proteins use more than one lipid anchor. A cytoplasmic tyrosine kinase, for example, is anchored with both myristic acid and palmitic acid. GPI-anchored proteins usually do not need a second anchor for stability. The GPI group has two fatty acyl groups that insert into the lipid bilayer. Its other end contains phosphoethanolamine, which links to target proteins involved in different cell functions.

Lipid Anchors in Membrane Proteins

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

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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...

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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...

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...

single-pass transmembrane proteins

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...

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 prenyl, fatty acyl, and GPI anchors attach proteins to the plasma membrane, including the CaaX motif and key enzyme steps.

Lipid Anchors in Membrane Proteins | 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.

Florida Department of Education

High School

Life Science

SC.912.L.18

SC.912.L.18.3

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9-12.B.1.2.a

Lipid Anchors in Membrane Proteins

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