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

最常见的三种脂质锚定基团是异戊二烯基团、脂肪酰基团以及糖基磷脂酰肌醇（GPI）锚定基团。
异戊二烯基团包括15个碳的法呢基和20个碳的格尔尼基格尔尼基团。它们与蛋白质羧基末端或其附近的半胱氨酸残基共价结合。
饱和的14碳肉豆蔻酸和16碳棕榈酸是与蛋白质结合最常见的脂肪酰基锚定分子。
肉豆蔻酸的添加，即肉豆蔻酰化，发生在蛋白质的N端甘氨酸残基上。蛋白质的棕榈酰化可发生在N端或C端的半胱氨酸残基上。
异戊二烯化、豆蔻酰化和棕榈酰化蛋白在细胞内信号转导通路及蛋白质-蛋白质相互作用中发挥着至关重要的作用。
GPI锚定结构连接于细胞外蛋白，其核心结构包含磷脂酰肌醇、葡糖胺、三个甘露糖和磷酸乙醇胺。
磷酸乙醇胺与目标蛋白的C端氨基酸结合，而磷脂则插入膜的外层。
这使得GPI锚定蛋白能够参与细胞外功能，例如细胞间通讯和细胞黏附。

作为锚的脂质

在细胞质膜中，形成双分子层的脂质也可以作为将蛋白质束缚在膜上的锚。在真核生物中所含有的三种主要脂质锚是-异戊二烯基团、脂肪酰基团和糖基磷脂酰肌醇（GPI）基团。异戊二烯基和脂肪酰基会在膜的细胞质表面发挥锚定物的作用，而糖基磷脂酰肌醇则会将蛋白质锚定在细胞的外侧。

大多数异戊二烯化蛋白质（例如 Ras 蛋白）中的羧基末端都含有 CaaX 基序或 CaaX 盒，其中的 “C” 代表了半胱氨酸，“a” 代表了任何脂肪族氨基酸，“X” 则代表了任何其他的氨基酸残留物。位于 “X” 处的氨基酸决定了与蛋白质的连接是用法尼基还是香叶基香叶醇来进行连接的。如果 “X” 是丙氨酸、丝氨酸、甲硫氨酸、半胱氨酸或谷氨酰胺，则法尼基转移酶会识别 CaaX 基序，并将法尼基与蛋白质进行连接。另一方面，如果 “X” 是谷氨酸或亮氨酸，那么 I 型香叶基香叶醇转移酶就会识别到 CaaX 基序，并将香叶基香叶醇附着到该基序上。在经过异戊二烯化后，三肽 aaX 将会被特定的蛋白酶去除，然后甲基转移酶会将由此产生带负电荷的半胱氨酸残基甲基化。甲基化能够去除半胱氨酸上的负电荷，并使其疏水。

有时会使用多个脂质锚来将蛋白质连接到膜上。例如，细胞质酪氨酸激酶就是借助肉豆蔻酸和棕榈酸锚定到膜上的。然而，GPI 锚定蛋白通常不需要另一中锚来对其进行稳定。GPI 的一端将会包含两个可以插入脂质双分子层的脂肪酰基。相反，另一端的磷酸乙醇胺则会附着在参与不同细胞功能的靶蛋白上。

在细胞质膜中，构成脂双层的脂质也可以作为锚定物，将蛋白质固定在膜上。三种主要类型的脂质锚定物……

Education

教育

JoVE Core

Cell Biology

细胞生物学

Unit 1

第一单元

Membrane Structure and Components

膜结构与组成

KEY TERMS AND CONCEPTS

关键术语与概念

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

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 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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ATP Energy Storage and Release

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1. Engage in evidence-based argument to relate a cell's function to the structure, function, and diversity of its components. Examples: Muscle cells have a large number of mitochondria, which create energy for contraction in the form of ATP. Some plant cells have a large vacuole which is used for storage and transport of excess nutrients in changing environments.

9-12.B.1.1

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Transcription Elongation Factors

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Pre-mRNA Processing: RNA Splicing

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Transfer RNA Synthesis

Ribosomal RNA Synthesis

The Nucleolus

Additional Subnuclear Structures

Translation

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Termination of Translation

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Nonsense-mediated mRNA Decay

The Eukaryotic Promoter Region

Molecular Chaperones and Protein Folding

Co-activators and Co-repressors

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lncRNA - Long Non-coding RNAs

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9-12.B.1.2

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9-12.B.1.2.a

Lipid Anchors in Membrane Proteins

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