Question

esearch the role of molecular chaperones (note, we didn’t cover this topic in class) and their role in protein folding and provide me a summary of (a) how they work, (b) where they are found and (c) if there are any diseases that have been identified where they don’t function appropriately.

Answer 1

The role of molecular chaperons ;

• A large group of unrelated protein families helps to assist folding or unfloding of other macro molecular structure.
• Folding of newly synthesized polypeptides in the crowded cellular environment requires the assistance of so-called molecular chaperone proteins.
• the chaperons are primarily concerned with protein folding.
• Role is to stabilize the unfolded proteins.
• Unfold them for the translocation across the membrane or the degradation or to assist in their correct assembly .
• They prevent inappropriate association of exposed hydrophobic surfaces and lead their substrate into productive folding.
• Some chaperones are non-specific, and interact with a wide variety of polypeptide chains, but others are restricted to specific targets.
• They often couple ATP binding/hydrolysis to the folding process.
• Molecular Chaperons interact with unfolded or partially folded subunits.

Role in Protein folding ; Molecular chaperones interact with unfolded or partially folded protein subunits, e.g. nascent chains emerging from the ribosome, or extended chains being translocated across subcellular membranes. They stabilize non-native conformation and facilitate correct folding of protein subunits.Most proteins fold into 3-D structures to gain functional activity. But in cellular environment ,newly formed proteins are at great risk in unfolding ,potentially forming toxic species. To avoid these risks cells invest in a network of molecular chaperons which helps to prevent aggregarion and promots perfect folding. Because protein molecules are highly dynamic, constant chaperone surveillance is required to ensure protein homeostasis . Nucleotide binding to ATP-dependent chaperones (e.g. GroEL, Hsp70, Hsp90) leads to sometimes large conformational changes in the chaperone which allow to shift between high and low affinity states for substrate proteins. The ATPase activity is tightly regulated by set of Co- chaperons. For ATP dependent chaperons the binding sites for nucleotides and protein are found in one protein.And in the case of ATP independent chaperons , the energy dependent step is performed by another chaperons.(Hsp70). therefore the ATP independent chaperons can be the efficient hoding components.

Chaperonins are characterized by a stacked double-ring structure and are found in prokaryotes, in the cytosol of eukaryotes, and in mitochondria. Other types of chaperones are involved in transport across membranes, for example membranes of the mitochondria and endoplasmic reticulum (ER) in eukaryotes.

Molecular chaperones interact with unfolded or partially folded protein subunits, e.g. nascent chains emerging from the ribosome, or extended chains being translocated across subcellular membranes. They stabilize non-native conformation and facilitate correct folding of protein subunits.Molecular chaperones are also termed “heat shock proteins” (HSPs), as initial studies found them to be upregulated in response to high temperatures. In eukaryotes, HSPs are a large and heterogeneous group of proteins that have been classified into families based on their molecular weight: Hsp40, Hsp60, Hsp70, Hsp90, Hsp100, and the small HSPs.

Dysfunction of any of these molecular chaperons can, lead to protein-misfolding disease.The first known protein-misfolding disease, the first inherited human disease to have a known molecular mechanism, was sickle cell anemia. In this disorder, a single point mutation changes a glutamic acid in the β-globulin chain of hemoglobin into a valine.