Protein folding defect

Case details

A 50-year-old male presents with “dancing –like” movements of his arms and progressive dementia. He cannot control the movement of his arms. He states that he knows that he has Huntington’s disease because his mother has the same disease. The disease is caused by abnormal protein folding.

Which of the following helps to mediate proper protein folding?

A. Chaperones

B. Transcription factors

C. DNA binding proteins

D. RNA binding proteins

E. All of the above.

Protein folding defect

 

Figure-Folding of a protein to acquire a mature functional conformation

Discussion- The correct answer is Chaperones.

Most proteins must fold into defined three-dimensional structures to gain functional activity.Protein folding generally occurs via a stepwise process (figure).

1) In the first stage, as the newly synthesized polypeptide emerges from the ribosomes, short segments fold into secondary structural units that provide local regions of organized structure.

2) In the second stage, the forces that drive hydrophobic regions into the interior of the protein away from solvent drive the partially folded polypeptide into a “molten globule” in which the modules of secondary structure rearrange to arrive at the mature conformation of the protein.

3) For oligomeric proteins, individual protomers tend to fold before they associate with other subunits.

In the cellular environment, newly synthesized proteins are at great risk of aberrant folding and aggregation, potentially forming toxic species. To avoid these dangers, cells invest in a complex network of molecular chaperones, which use ingenious mechanisms to prevent aggregation and promote efficient folding.

Chaperone proteins participate in the folding of over half of mammalian proteins. The hsp70 (70-kDa heat shock protein) family of chaperones bind short sequences of hydrophobic amino acids in newly synthesized polypeptides, shielding them from solvent. Chaperones prevent aggregation, thus providing an opportunity for the formation of appropriate secondary structural elements and their subsequent coalescence into a molten globule. The hsp60 family of chaperones, sometimes called chaperonins, differs in sequence and structure from hsp70 and its homologs. Hsp60 act later in the folding process, often together with an hsp70 chaperone. The central cavity of the donut-shaped hsp60 chaperone provides a sheltered environment in which a polypeptide can fold until all hydrophobic regions are buried in its interior, eliminating aggregation.

Because protein molecules are highly dynamic, constant chaperone surveillance is required to ensure protein homeostasis (proteostasis). An age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer’s disease and Parkinson’s disease.

As regards other options

DNA binding proteins are required for various processed such as replication, transcription, translation, regulation of gene expression and repair of DNA damage, but they are not required for protein folding.

RNA binding proteins and transcription factors are required for the process of transcription; they have no role in protein folding.

Please help Biochemistry for Medics by "CLICKING ON THE ADVERTISEMENTS" every time you visit us. Thank you!

Leave a Reply

Copy Protected by Chetan's WP-Copyprotect.