Protein Structure and Sickle Cell Disease (Lecture Notes)

Vocabulary-style flashcards covering key terms and concepts from the notes on sickle cell disease, amino acids, protein structure, and hemoglobin.

Sickle Cell Disease

A recessive inherited blood disorder caused by a single amino acid mutation in the HBB gene, leading to sickled red blood cells and symptoms such as anemia, dactylitis, infections, and acute chest syndrome.

HBB gene

Hemoglobin beta chain gene where a single mutation causes sickle cell disease.

Sickle erythrocytes

Red blood cells that take on a sickle shape due to hemoglobin abnormalities.

Anemia

Low healthy red blood cell count, a common symptom of sickle cell disease.

Acute chest syndrome

A serious complication of sickle cell disease involving chest pain and respiratory symptoms.

Dactylitis

Painful swelling of the hands and feet, commonly seen in young children with sickle cell disease.

Prevalence in the U.S.

Approximately 90,000–100,000 cases of sickle cell disease in the United States.

African American births risk

About 1 in 500 African American births are affected by sickle cell disease.

Amino acids

Building blocks (monomers) of proteins (polymers).

Monomers

Small units that link to form polymers, such as amino acids in proteins.

Amine group

The basic –NH2 group on amino acids (pKa > 9).

Carboxyl group

The acidic –COOH group on amino acids (pKa < 3).

Side chain (R group)

The group that gives each amino acid its unique properties.

Zwitterion

Molecule carrying both positive and negative charges at physiological pH.

Physiological pH

Around 7.4, where amino acids commonly exist as zwitterions.

Hydrophilic

Water-loving; amino acids that interact with water (charged or polar).

Hydrophobic

Water-fearing; residues that tend to be buried inside proteins or away from water.

Aromatic side chains

Ring-containing residues (phenylalanine, tryptophan, tyrosine).

Aliphatic side chains

Non-ring residues (alanine, leucine, valine).

Phosphorylatable residues

Can accept phosphate groups (serine, threonine, tyrosine).

Disulfide bond

S–S bond between two cysteines; forms in oxidizing environments and stabilizes protein structure.

Cysteine

Amino acid that forms disulfide bonds.

Proline

Amino acid with a rigid ring that induces kinks in protein chains.

Peptides

Linear chains of amino acids linked by peptide bonds.

Peptide bonds

Amide bonds linking amino acids; bonds are rigid and planar with limited rotation.

N-terminus

The start end of a peptide chain; direction from N-terminus to C-terminus.

C-terminus

The end of a peptide chain.

Primary structure

The linear sequence of amino acids from N-terminus to C-terminus; conserved across species and may have isoforms.

Secondary structure

Local shapes like helices and sheets stabilized by hydrogen bonds.

Tertiary structure

The overall three-dimensional shape of a single polypeptide chain.

Hydrogen bonds

Weak attractions between a hydrogen bound to an electronegative atom and another electronegative atom; stabilize secondary structure.

Folding

Process by which a polypeptide attains its functional three-dimensional shape.

Hydrophobic interactions

Driving force for folding; hydrophobic residues cluster away from water, reducing disruption to water structure.

Entropy (hydrophobic effect)

Water near hydrophobic surfaces is ordered, so hydrophobic clustering increases overall entropy by reducing structured water.

Membrane formation

Hydrophobic interactions contribute to the assembly of cellular membranes.

Electrostatic interactions

Interactions between charged groups; include ionic bonds and dipole-dipole interactions, stabilizing protein conformations.

Ionic (electrostatic) bonds

Charge-based bonds affected by salt; can stabilize or destabilize structures.

Dipole–dipole interactions

Attractive forces between molecular dipoles; hydrogen bonds are a common example in proteins.

Quaternary structure

Assembly of multiple polypeptide chains into a functional complex.

α2β2 tetramer

Hemoglobin quaternary structure consisting of two alpha and two beta subunits.

Hemoglobin assembly

Subunits interact via numerous contacts, enabling cooperative oxygen binding.

Lys and Arg

Positively charged amino acids that stabilize subunit interfaces.

Glu and Asp

Negatively charged amino acids involved in intersubunit electrostatics.

Cooperative oxygen binding

Hemoglobin property where binding of oxygen at one site increases affinity at remaining sites.

Heme group

Iron-containing prosthetic group in hemoglobin that binds oxygen.

Iron (Fe) in heme

Iron atom central to the heme group that binds and releases oxygen.

Hemoglobin mass in RBCs

Hemoglobin makes up about 95% of the dry mass of red blood cells.

Glu to Val mutation at β-chain position 7

E7V mutation in the β-globin chain responsible for sickle cell disease.