Q.45 The sequence of a polypeptide that forms a transmembrane helix is shown below.
Which one of the following segments of the peptide is most likely to span the membrane?
(A) E3-G22
(B) V5-A25
(C) E15 −A34
(D) F21-R40

Question Overview

A polypeptide sequence that forms a transmembrane α-helix is shown below:

Question:
Which of the following segments of the peptide is most likely to span the membrane?

Options:

• (A) E3–G22

• (B) V5–A25

• (C) E15–A34

• (D) F21–R40

Key Concept: What Makes a Transmembrane Helix?

A transmembrane α-helix typically has:

1. 20–25 amino acids (to span ~30 Å lipid bilayer)

2. High hydrophobic amino acid content
   (Leu, Ile, Val, Ala, Gly, Phe)

3. Minimal charged or polar residues

4. Often positively charged residues (Arg/Lys) near the cytosolic end (positive-inside rule)

Hydrophobic Core in the Given Sequence

The most hydrophobic stretch in the sequence is:

This region:

• Is rich in Val, Ile, Ala, Gly, Leu

• Forms a continuous hydrophobic stretch

• Is of sufficient length to span the lipid bilayer

Correct Answer

✅ Correct Option: (C) E15–A34

Explanation of Each Option

Option (A): E3–G22 ❌ Incorrect

• Contains many polar and charged residues:

  • E (Glu), R (Arg), H (His), Q (Gln)

• Hydrophobic stretch is too short

• Not suitable for stable membrane insertion

Option (B): V5–A25 ❌ Incorrect

• Includes several hydrophilic residues (E, Q, H)

• Only partially overlaps with the hydrophobic region

• Length and composition are suboptimal

Option (C): E15–A34 ✅ Correct

• Encompasses the entire hydrophobic core

• Length ≈ 20 amino acids, ideal for membrane thickness

• Dominated by nonpolar residues

• Best matches known transmembrane helix characteristics

✔ Most stable and energetically favorable membrane-spanning segment

Option (D): F21–R40 ❌ Incorrect

• Although hydrophobic at the start, it ends with:

  • Arg (R), Lys (K) → charged residues

• Charged residues disrupt membrane-spanning helices

• More likely part of a membrane-proximal or cytosolic region

Final Answer

🟢 The segment most likely to span the membrane is:

(C) E15–A34