In protein post-translational modification, what is the consensus sequence motif for N-linked glycosylation (attachment of an N-linked oligosaccharide to asparagine) within a polypeptide chain?

Difficulty: Easy

Correct Answer: Asn-Xaa-(Ser or Thr)

Explanation:


Introduction / Context:
N-linked glycosylation is a major co-/post-translational modification in eukaryotes where an oligosaccharide is attached to the side chain amide nitrogen of asparagine. Recognizing the canonical sequence motif helps in predicting glycoprotein sites and understanding folding, trafficking, and function of membrane and secretory proteins.


Given Data / Assumptions:

  • The question asks for the consensus amino-acid sequence around the modified residue.
  • “Consensus” indicates a motif frequently recognized by the oligosaccharyltransferase complex in the endoplasmic reticulum.
  • Standard single-letter position notation: Asn at position 1, any residue (Xaa) at position 2, and Ser or Thr at position 3.


Concept / Approach:
The well-established motif is Asn-Xaa-Ser/Thr, often written as N-X-S/T. The central position (Xaa) can be almost any residue except proline because proline imposes conformational constraints that reduce enzyme recognition. While not every NXS/T site is glycosylated, most verified N-glycans occur within this sequence context.


Step-by-Step Solution:

1) Identify candidate motifs that place Asn (N) at the glycosylation site.2) Check whether the third position is Ser or Thr, which supplies the required hydroxyl for recognition (though the glycan is on Asn).3) Ensure the middle residue is permissive (any residue except Pro preferred).4) Conclude the consensus is Asn-Xaa-(Ser/Thr).


Verification / Alternative check:
Biochemical mapping and mass spectrometry of glycopeptides repeatedly validate N-X-S/T as the dominant ER cotranslational consensus motif; mutation of any position often abolishes glycosylation.


Why Other Options Are Wrong:

  • (Ser or Thr)-Asn-Ala: places Asn in the wrong position.
  • Thr-(Asn or Gln)-Ala: incorrect order and includes Gln, which is not used for N-linkage.
  • None of these: a correct consensus exists.
  • Asn-Pro-(Ser or Thr): proline at X disrupts the motif and typically prevents glycosylation.


Common Pitfalls:
Confusing O-glycosylation (on Ser/Thr) with N-glycosylation (on Asn), or assuming every N-X-S/T site is necessarily occupied—context and structure also matter.


Final Answer:
Asn-Xaa-(Ser or Thr)

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