12.9
Lípidos como anclas
En la membrana plasmática, los lípidos que forman la bicapa también pueden actuar como ancla para unir las proteínas a la membrana. Los tres tipos pri…
Los tres tipos más comunes de anclajes lipídicos son los grupos prenil, los grupos acilo grasos y los anclajes glicosilfosfatidilinositol o GPI.
Los grupos prenyl son los grupos farnesilo de 15 carbonos y geranilgeranyl de 20 carbonos. Se unen a los residuos de cisteína en o cerca del extremo carboxilado de las proteínas.
El ácido mirístico saturado de 14 carbonos y el ácido palmítico de 16 carbonos son los anclajes de acilo graso más comunes unidos a las proteínas.
La adición de ácido mirístico, o miristoilación, ocurre en el residuo de glicina N-terminal de una proteína. La palmitoilación de las proteínas puede ocurrir en el residuo de cisteína terminal N o C.
Las proteínas preniladas, miristoiladas y palmitoiladas desempeñan un papel esencial en las vías de señalización intracelular y en las interacciones proteína-proteína.
Los anclajes GPI se adhieren a proteínas extracelulares y contienen una estructura central de fosfatidilinositol, glucosamina, tres manosas y fosfoetanolamina.
La fosfoetanolamina se une al aminoácido C-terminal de la proteína objetivo y el fosfolípido se inserta en la capa externa de la membrana.
Esto permite que las proteínas ancladas a GPI participen en funciones extracelulares como la comunicación célula-célula y la adhesión celular.
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Q1: What are the three main types of lipid anchors found in eukaryotic membranes?
The three main types are prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol (GPI) anchors. Prenyl and fatty acyl groups anchor proteins on the cytosolic surface of the membrane, while GPI anchors attach proteins to the extracellular side. Each type uses different chemical linkages and serves distinct cellular functions.
Q2: How do prenyl groups attach to proteins and what determines the type of prenylation?
Prenyl groups bond to cysteine residues at or near the protein's carboxy terminus through a CaaX motif. The amino acid at the X position determines whether farnesyl transferase attaches a 15-carbon farnesyl group or geranylgeranyl transferase attaches a 20-carbon geranylgeranyl group. After prenylation, proteases remove the tripeptide, and methylation makes the cysteine hydrophobic.
Q3: What is the difference between myristoylation and palmitoylation?
Myristoylation adds a 14-carbon myristic acid to a protein's N-terminal glycine residue, while palmitoylation adds a 16-carbon palmitic acid to N- or C-terminal cysteine residues. Both are saturated fatty acyl anchors that tether proteins to the membrane. Proteins can use both modifications simultaneously for stronger membrane attachment.
Q4: How do GPI anchors differ from prenyl and fatty acyl anchors in their membrane orientation?
GPI anchors attach to extracellular proteins on the outer membrane layer, whereas prenyl and fatty acyl anchors position proteins on the cytosolic surface. GPI anchors contain a core structure of phosphatidylinositol, glucosamine, three mannoses, and phosphoethanolamine, with the phospholipid inserting into the bilayer and the phosphoethanolamine bonding to the protein's C-terminal amino acid.
Q5: What cellular functions do lipid-anchored proteins perform?
Prenylated, myristoylated, and palmitoylated proteins play essential roles in intracellular signaling pathways and protein-protein interactions. GPI-anchored proteins participate in extracellular functions such as cell-cell communication and cell adhesion. These lipid anchors enable proteins to interact with membrane lipids and other membrane components effectively.
Q6: Why do some proteins require multiple lipid anchors?
Some proteins use more than one lipid anchor to achieve stronger and more stable membrane attachment. For example, cytoplasmic tyrosine kinase is anchored using both myristic and palmitic acid simultaneously. However, GPI-anchored proteins typically do not require additional anchors because their two fatty acyl groups and phosphoethanolamine linkage provide sufficient stabilization.
Q7: What is the CaaX motif and how does it determine prenylation specificity?
The CaaX motif is a recognition sequence at the carboxy-terminal of prenylated proteins where C is cysteine, a represents any aliphatic amino acid, and X is any other amino acid. If X is alanine, serine, methionine, cysteine, or glutamine, farnesyl transferase recognizes it and attaches farnesyl. If X is glutamic acid or leucine, geranyl transferase type I attaches geranylgeranyl instead.