12.9
Lipídios como âncoras
Na membrana plasmática, os lipídios que formam a bicamada também podem atuar como uma âncora para prender as proteínas à membrana. Os três principais…
Os três tipos mais comuns de âncoras lipídicas são grupos prenil, grupos acila gordurosa e âncoras glicosilfosfatidilinositol ou GPI.
Os grupos prenil são os grupos farnesil de 15 carbonos e os grupos geranilgeranil de 20 carbonos. Eles se ligam a resíduos de cisteína no terminal carboxi das proteínas ou próximo a ele.
O ácido mirístico de 14 carbonos saturado e o ácido palmítico de 16 carbonos são as âncoras de acila graxa mais comuns ligadas às proteínas.
A adição de ácido mirístico, ou miristoilação, ocorre no resíduo de glicina N-terminal de uma proteína. A palmitoilação das proteínas pode ocorrer no resíduo de cisteína N- ou C-terminal.
As proteínas preniladas, miristoiladas e palmitoiladas desempenham um papel essencial nas vias de sinalização intracelular e nas interações proteína-proteína.
As âncoras GPI se ligam a proteínas extracelulares e contêm uma estrutura central de fosfatidilinositol, glucosamina, três manonoses e fosfoetanolamina.
A fosfoetanolamina se liga ao aminoácido C-terminal da proteína alvo e o fosfolipídio se insere na camada externa da membrana.
Isso permite que as proteínas ancoradas em GPI participem de funções extracelulares, como comunicação célula-célula e adesão 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.