Lipid Anchoring of Cytosolic Proteins

Many water-soluble proteins in eukaryotic cells are attached to the plasma membrane through covalently linked lipids. This lipid modification helps to anchor these proteins to the membrane surface without requiring a transmembrane domain. There are several types of lipid modifications that serve this anchoring function, including myristoylation, palmitoylation, and prenylation.

N–terminal Myristoylation

One common type of fatty acylation is the attachment of a myristate group (a saturated 14–carbon fatty acid) to a protein. This modification typically occurs at the N–terminus of the polypeptide chain. For myristoylation to occur, the N–terminal amino acid is usually Glycine.

• The myristate group is attached via an amide linkage to the α–amino group of the N–terminal Glycine residue.
• This modification often happens co–translationally, meaning it occurs while the protein is still being synthesized on the ribosome.
• Proteins modified in this way include various kinases (e.g., c–Src), signal transduction proteins, and viral proteins.

Palmitoylation

Palmitoylation involves the attachment of a palmitate group (a saturated 16–carbon fatty acid). Unlike myristoylation, palmitoylation is typically reversible and can occur at various positions within a protein, often on cysteine residues via a thioester linkage. However, the question specifically mentions attachment by a fatty acyl group to amino acids at the N–terminus, and while palmitoylation *can* happen near the N-terminus, N-terminal *myristoylation* on Glycine is a classic example of N-terminal fatty acylation for membrane anchoring as described.

Amino Acid Specificity

Let's consider the options provided in the context of N–terminal fatty acylation for membrane anchoring:

• Glycine: As discussed, N–terminal myristoylation specifically requires Glycine as the N–terminal amino acid. This modification serves as a stable lipid anchor.
• Tyrosine: Tyrosine residues are commonly modified by phosphorylation, not typically by fatty acylation at the N–terminus for membrane anchoring.
• Serine: Serine residues are commonly modified by phosphorylation or glycosylation, not typically by fatty acylation at the N–terminus for membrane anchoring.
• Lysine: Lysine residues can be modified by ubiquitination, acetylation, or sumoylation. While lysine side chains can potentially be acylated, N–terminal fatty acylation for membrane anchoring as described in the question is strongly associated with Glycine.

Therefore, the amino acid generally found at the N–terminus for anchoring cytosolic proteins to the plasma membrane by a fatty acyl group like myristate is Glycine.