Protein Folding Mechanisms

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Questions and Answers

What percentage of a myoglobin polypeptide chain is estimated to be folded into alpha helices?

90%

80% (correct)

60%

70%

Which amino acid residues predominantly form the interior of the myoglobin molecule?

Nonpolar amino acids (correct)

Polar amino acids

Charged amino acids

Aromatic amino acids

What stabilizes the β-bends and loops in myoglobin?

Disulfide bridges

Hydrophobic interactions

Peptide bonds

Hydrogen bonds and ionic bonds (correct)

Where is the heme group located within the myoglobin molecule?

In a crevice lined with nonpolar amino acids Signup and view all the answers

What is the role of the proximal histidine in myoglobin?

Binds directly to the iron of heme Signup and view all the answers

What is the primary function of hemoglobin?

Transport oxygen Signup and view all the answers

What type of interaction primarily stabilizes the interior structure of myoglobin?

Hydrophobic interactions Signup and view all the answers

Which histidine residue helps stabilize the binding of oxygen to iron in myoglobin without directly interacting with the heme?

Distal histidine Signup and view all the answers

What kind of bonds do polar amino acids on the surface of myoglobin primarily form?

Hydrogen bonds Signup and view all the answers

What is one key characteristic of mouse myoglobin double knockouts?

They show an apparently normal phenotype. Signup and view all the answers

What is the primary function of chaperones during protein folding?

To prevent premature folding of polypeptides Signup and view all the answers

What term is used to refer to proteins that consist of more than one polypeptide chain?

Multimeric proteins Signup and view all the answers

How are subunits in a protein's quaternary structure primarily held together?

Noncovalent interactions Signup and view all the answers

What are isozymes?

Proteins that perform the same function but have different structures Signup and view all the answers

What happens to misfolded proteins in a cell under normal circumstances?

They are tagged and degraded Signup and view all the answers

What can lead to the formation of amyloid diseases?

Abnormal proteolytic cleavage Signup and view all the answers

What does the central cavity in chaperonins assist with?

Stabilizing hydrophobic interactions in nascent polypeptides Signup and view all the answers

Which type of interactions primarily facilitate the cooperative function in hemoglobin?

Noncovalent interactions Signup and view all the answers

How do deposits of misfolded proteins relate to aging?

They can accumulate due to imperfections in quality control Signup and view all the answers

Which amino acids are classified as charged amino acids?

Glutamate, aspartate, lysine, arginine Signup and view all the answers

What type of bonding stabilizes the β-sheet structure?

Interchain and intrachain hydrogen bonds Signup and view all the answers

Which statement is true for the α-helix?

It is stabilized solely by intrachain hydrogen bonds. Signup and view all the answers

Which best describes the neurotoxic aggregates found in Alzheimer disease?

They are fibrillar protein assemblies containing β-pleated sheets. Signup and view all the answers

How does Alzheimer disease primarily develop in the brain?

By the buildup of β-amyloid peptide aggregates. Signup and view all the answers

What can be inferred about the relationship of Alzheimer's disease to genetics?

It may involve genetic predisposition along with environmental factors. Signup and view all the answers

In comparison to the α-helix, what is a distinguishing feature of the β-sheet?

It can form between different polypeptide chains. Signup and view all the answers

Which trait is commonly observed in proteins exhibiting β-sheet structures?

They can exist in both globular and fibrous forms. Signup and view all the answers

What is a functional consequence of charged amino acids in protein structure?

They can disrupt conformational stability. Signup and view all the answers

What role does amyloid precursor protein play in Alzheimer's disease?

It contributes to the buildup of β-amyloid aggregates. Signup and view all the answers

What does the ζ gene express during early development?

α-globin-like component of embryonic hemoglobin Signup and view all the answers

How many β-globin-like genes are present alongside the β-globin chain gene on chromosome 11?

Four Signup and view all the answers

What is removed from the mRNA precursor sequence during the process of gene expression?

Introns Signup and view all the answers

Which of the following conditions is NOT considered a hemoglobinopathy?

Hemophilia Signup and view all the answers

What type of genetic disorder is characterized by the production of an abnormal hemoglobin molecule?

Hemoglobinopathy Signup and view all the answers

What occurs after the mature mRNA enters the cytosol?

It is translated to produce a globin chain. Signup and view all the answers

What is the primary hemoglobin found in fetuses during the last months of fetal life?

HbF Signup and view all the answers

What is the composition of fetal hemoglobin (HbF)?

Two α chains and two γ chains Signup and view all the answers

When does HbA start to replace HbF in developing infants?

At about the eighth month of pregnancy Signup and view all the answers

What structural change occurs to hemoglobin during the transition from HbF to HbA?

Change in γ chains to β chains Signup and view all the answers

Why does HbF have a higher affinity for oxygen compared to HbA?

It only weakly binds 2,3-BPG Signup and view all the answers

What is the composition of human hemoglobin A (HbA)?

Two α and two β chains Signup and view all the answers

Which hemoglobin type is synthesized at low levels in adults compared to HbA?

HbA2 Signup and view all the answers

What is the significance of the α-chains in normal adult human hemoglobins?

They are identical in structure across different types Signup and view all the answers

Where is the primary site of globin synthesis during early fetal development?

Embryonic yolk sac Signup and view all the answers

What happens to the oxygen affinity of hemoglobin when carbon monoxide (CO) binds to it?

Increases Signup and view all the answers

Study Notes

Protein Folding and Chaperonins

Partially folded proteins enter chaperonin structures, binding through hydrophobic interactions before being released in a functional form.
Chaperonins, or cage-like chaperones, stabilize nascent and denatured proteins to prevent premature folding and aggregation.

Quaternary Structure of Proteins

Proteins can be monomeric (single polypeptide) or oligomeric (multiple polypeptides), with their arrangement referred to as quaternary structure.
Noncovalent interactions (hydrogen bonds, ionic bonds, hydrophobic interactions) primarily hold subunits together.
Isoforms perform similar functions with different primary structures, arising from gene variations or tissue-specific processing; enzymes among these are called isozymes.

Protein Misfolding and Disease

Misfolded proteins may accumulate due to incomplete cellular quality control systems, leading to intracellular or extracellular aggregates.
Accumulation of misfolded proteins is linked to diseases such as Alzheimer's disease, characterized by common deposits.

Alzheimer's Disease

Associated with accumulation of neurotoxic amyloid β peptide aggregates resulting from the abnormal processing of amyloid precursor protein.
Noted for causing cognitive decline, mood alterations, and memory loss, especially prevalent in aging individuals.

Myoglobin Structure and Function

Myoglobin is a compact protein with ~80% of its structure forming α-helices, stabilized by prolines and hydrogen bonds.
Nonpolar amino acids dominate the interior, stabilizing the structure via hydrophobic interactions, while polar amino acids are located on the surface for hydrogen bonding.

Hemoglobin Structure and Variants

Hemoglobin, present exclusively in red blood cells, transports oxygen from lungs to tissues, modulating availability of nitric oxide which influences blood vessel diameter.
Different hemoglobin variants, such as HbA (adult), HbF (fetal), and HbA2, arise through gene expression timing and quantitative synthesis.

Fetal Hemoglobin (HbF)

HbF consists of two α and two γ chains; it is synthesized predominantly during fetal development to enhance oxygen affinity.
Binding of 2,3-BPG is weak in HbF, contributing to its higher oxygen affinity compared to adult hemoglobin (HbA).

Hemoglobinopathies

Defined as genetic disorders leading to abnormal or insufficient normal hemoglobin production, such as sickle cell anemia, hemoglobin C disease, and thalassemias.
Sickle cell anemia and hemoglobin C disease result from qualitative changes in hemoglobin structure, while thalassemias involve quantitative production deficiencies.

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Description

This quiz explores the intricate processes involved in protein folding, focusing on the role of chaperones and chaperonins in preventing improper protein aggregation. Understand how partially folded proteins interact with their environment and the significance of hydrophobic interactions in biological systems.