Protein folding mechanisms: Which statement best captures how newly made polypeptides achieve native structure in cells?

Introduction / Context:
How proteins fold into precise three-dimensional structures is central to biochemistry. While the primary sequence encodes the native state, cells rely on a proteostasis network — especially molecular chaperones — to achieve efficient and accurate folding in the crowded cytosol.

Given Data / Assumptions:

• Newly synthesized chains emerge from ribosomes into a crowded environment.
• Molecular chaperones (e.g., Hsp70, Hsp60/GroEL–GroES) assist folding and prevent aggregation.
• Question asks which statement best describes cellular folding.

Concept / Approach:
Anfinsen’s dogma states that sequence determines structure under ideal conditions. In vivo, however, co-translational folding and chaperone assistance are crucial to avoid kinetic traps and aggregation. Thus, the best answer emphasizes chaperone mediation rather than ribosomes or purely spontaneous folding.

Step-by-Step Solution:

Verification / Alternative check:
Loss or inhibition of chaperones increases aggregates and misfolded proteins; overexpression rescues folding of metastable proteins, supporting their essential role.

Why Other Options Are Wrong:

• “Automatic only by sequence” ignores the in vivo need for chaperones.
• Ribosomes synthesize polypeptides but do not actively fold them into native structures.
• “None” is incorrect because chaperone mediation is well established.

Common Pitfalls:
Presenting “spontaneous vs. assisted” as mutually exclusive; both are true but chaperone assistance is the defining cellular feature for many proteins.

Final Answer:
Folding is mediated by helper proteins known as molecular chaperones