4. Protein Structure & Function – Amino-Acid Changes and Folding

Vocabulary flashcards covering key terms related to how amino-acid changes influence protein folding, stability, and associated diseases.

Protein folding

The process by which a linear polypeptide chain acquires a specific, biologically active three-dimensional structure.

Amino-acid sequence

The linear order of amino acids in a protein that dictates its final structure and function.

Minimum length for folding

≈70 amino acids are generally required for a polypeptide to stably fold into a defined structure.

Hydrophobic interaction

Non-polar side chains cluster away from water, driving folding and stabilizing a protein’s interior.

Hydrogen bond (in proteins)

An attraction between an electronegative atom (O or N) and hydrogen, helping stabilize secondary and tertiary structures.

Charged side-chain repulsion

Electrostatic repelling forces between like-charged residues (e.g., Glu–Glu or Lys–Lys) that can hinder α-helix formation.

α-Helix constraint: electrostatics

Attraction or repulsion between successive charged residues can promote or destabilize helix formation.

α-Helix constraint: bulkiness

Large adjacent side chains create steric hindrance that destabilizes a helix.

α-Helix constraint: i + 3/i + 4 interactions

Side chains three or four residues apart interact, affecting helix stability.

Proline effect

Proline’s rigid ring and lack of amide hydrogen break or kink α-helices and disrupt folding.

Glycine flexibility

Small, non-chiral glycine allows high backbone mobility, favoring coils or loops rather than rigid helices.

Disulfide bond

Covalent linkage between two cysteine residues that stabilizes tertiary structure.

Primary structure

The linear sequence of amino acids in a polypeptide chain.

Tertiary structure

The overall three-dimensional folding of a single polypeptide, including interactions among secondary structures.

Point mutation

Single nucleotide change in DNA that can substitute one amino acid, potentially altering protein function.

Sickle cell anemia

Disease caused by Glu6→Val mutation in β-globin, leading to abnormal hemoglobin aggregation.

Hemoglobin C

Variant hemoglobin from Glu6→Lys mutation in β-globin, causing mild hemolytic anemia.

Tay-Sachs disease

Neurodegenerative disorder from various point mutations in HEXA, altering a single amino acid in Hexosaminidase A.

Cystic fibrosis

Condition in which deletion of three nucleotides in CFTR removes Phe508, producing misfolded chloride channel protein.

Fibrodysplasia Ossificans Progressiva (FOP)

Bone-forming disorder due to Arg202→His mutation in ACVR1 receptor.

Scurvy

Collagen disorder from vitamin C deficiency that decreases proline hydroxylation, weakening connective tissue.

Huntington disease

Neurodegenerative disease caused by expansion of a polyglutamine (CAG) tract in huntingtin protein.

Gaucher’s disease

Lysosomal disorder; point mutations such as N370S or L444P in β-glucocerebrosidase impair enzyme folding/function.

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)

Membrane protein whose ΔPhe508 mutation leads to misfolding and cystic fibrosis.