Protein Structure and Function

Protein Structure and Function

• Proteins have different levels of structure, including primary, secondary, tertiary, and quaternary structures, each stabilized by specific forces.
• Primary structure: the linear sequence of amino acid residues joined through peptide bonds, determining the 3D structure of a polypeptide.
• Peptide bonds: formed through condensation reactions between α-carboxylate and α-amino groups, with characteristics that affect protein structure, such as restricted rotation and resonance.
• Chemical nature of amino acids: classified into aliphatic, non-aromatic with hydroxyl R-groups, sulfur-containing, acidic, basic, aromatic, imino, and other groups.

Primary Structure

• Nonpolar (aliphatic) side groups: gly, ala, ile, leu, val, met, and pro.
• Side chains with basic groups: arg, lys, and his.
• Side chains with acidic groups: asp and glu.
• Polar but uncharged groups: amide derivatives of asp and glu (asn and gln), hydroxyl groups (ser, thr, and tyr), and sulfhydryl groups (cys).
• Other classifications: hydrophilic vs hydrophobic, optical properties, essential vs non-essential, and glucogenic vs ketogenic or ketogenic/glucogenic.

Secondary Structure

• H-bonding of peptide backbone causes amino acids to fold into a repeating pattern, forming common structures like α-helix and β-sheet.
• β-sheet: stabilized by hydrogen bonds co-planar with the β-pleat, with R groups alternating above and below the plane.
• Super secondary structures (motifs): combining secondary structural elements, such as the αβ motif, to form globular proteins.

Tertiary Structure

• Final folded state of a complete polypeptide in 3D conformation, stabilized by hydrophobic interactions, hydrogen bonding, ionic interactions, and disulfide bond formation.
• Creates specific and flexible binding sites for ligands and maintains an appropriate surface for the protein's cellular location.
• Folding can be affected by post-translational modifications of amino acids, such as phosphorylation, glycosylation, and acetylation.

Protein Domains

• Fundamental functional and three-dimensional structural unit(s) of a polypeptide, comprising one or more super-secondary structures.
• Folding of a domain usually occurs independently of folding in other domains.
• A domain is a conserved part of a given full-length protein sequence, with a defined tertiary structure that can evolve, function, and exist independently of the rest of the protein chain.

Protein Folding and Quaternary Structure

• Protein folding requires energy and is assisted by chaperone proteins, which protect and guide the proper folding of nascent polypeptide chains.
• Quaternary structure: multiple polypeptide chains (or subunits) assembled into a supramolecular complex, with a specific number of subunits designated by a prefix (e.g., dimeric, trimeric).
• May consist of identical (homopolymeric) or different (heteropolymeric) subunits.

Protein Misfolding and Function

• Protein misfolding alters normal function and interactions of proteins, as seen in sickle cell anemia, where a mutation in the β chain changes the quaternary structure of hemoglobin.

Fibrous Proteins

• Elongated, rigid proteins enriched in specific amino acids and unique secondary structures, serving structural functions in the body.
• Examples: collagen, which provides tensile strength, with a superfamily of extracellular matrix proteins.

Collagen

• Most abundant protein in the body, with a triple helix of three α-polypeptides wound around each other.
• Primary structure: polymer of (Gly-X-Y) repeats, where X is frequently proline and Y is often hydroxyproline (or hydroxylysine).
• Vitamin C is required as a cofactor for the hydroxylation of Pro and Lys.

Explore the different levels of protein structure, including primary, secondary, tertiary, and quaternary structures, and learn how they are stabilized by specific forces.