Proteins are the workhorses of cells, performing countless functions. Their structure, from amino acid sequences to complex 3D shapes, determines how they work. Understanding protein structure is key to grasping how these molecules carry out their vital roles in living organisms.

Proteins don't act alone. They interact with other molecules, undergo changes, and are regulated in various ways. This dynamic nature allows proteins to respond to cellular needs, catalyze reactions as enzymes, and form the basis of many biological processes essential for life.

Protein Structure

Hierarchical Levels of Protein Structure

• Primary structure forms the foundation of protein architecture consisting of a linear sequence of amino acids
• Secondary structure emerges from hydrogen bonding between amino acids creating regular patterns (alpha helices, beta sheets)
• Tertiary structure results from folding and interactions between secondary structures producing a three-dimensional conformation
• Quaternary structure arises when multiple polypeptide chains combine to form a functional protein complex
• Protein folding involves the process by which a protein assumes its functional three-dimensional shape driven by various forces (hydrophobic interactions, hydrogen bonding, van der Waals forces)

Factors Influencing Protein Structure

• Amino acid sequence determines the unique folding pattern of each protein
• Hydrogen bonds stabilize secondary structures by forming between the carbonyl oxygen and amide hydrogen of peptide bonds
• Disulfide bridges form covalent bonds between cysteine residues contributing to tertiary structure stability
• Hydrophobic interactions drive the formation of a protein's hydrophobic core burying non-polar amino acids
• Chaperone proteins assist in proper folding preventing aggregation and misfolding of newly synthesized proteins

Structural Motifs and Domains

• Alpha helices consist of coiled structures with 3.6 amino acids per turn stabilized by hydrogen bonds
• Beta sheets comprise extended strands of amino acids connected by hydrogen bonds between adjacent strands
• Beta turns allow polypeptide chains to reverse direction facilitating compact protein folding
• Protein domains represent distinct functional or structural units within a larger protein (DNA-binding domains, catalytic domains)
• Structural motifs represent recurring patterns of secondary structure elements (helix-turn-helix, zinc finger)

Protein Interactions and Regulation

Protein-Protein Interactions

• Protein-protein interactions form the basis of many cellular processes and signaling pathways
• Binding interfaces involve complementary surfaces with specific chemical and physical properties
• Weak non-covalent interactions (hydrogen bonds, van der Waals forces) collectively stabilize protein complexes
• Protein interaction networks map the interconnections between proteins in cellular systems
• Techniques for studying protein interactions include yeast two-hybrid systems and co-immunoprecipitation

Allosteric Regulation and Conformational Changes

• Allosteric regulation involves binding of molecules at sites distant from the active site
• Conformational changes induced by allosteric effectors alter protein activity or binding affinity
• Positive allosteric modulators enhance protein activity while negative modulators inhibit it
• Hemoglobin exhibits cooperative binding of oxygen molecules through allosteric regulation
• Allosteric enzymes demonstrate altered kinetics in response to regulatory molecules

Post-Translational Modifications

• Post-translational modifications alter protein properties after synthesis
• Phosphorylation adds phosphate groups to specific amino acids (serine, threonine, tyrosine) affecting protein activity
• Glycosylation attaches sugar moieties to proteins influencing stability and cellular localization
• Ubiquitination tags proteins for degradation by the proteasome system
• Acetylation modifies lysine residues impacting protein-DNA interactions and gene expression
• Proteolytic cleavage activates or inactivates proteins by removing specific segments

Enzymes

Enzyme Structure and Function

• Enzymes act as biological catalysts accelerating chemical reactions without being consumed
• Active sites form specialized pockets where substrates bind and reactions occur
• Substrate specificity results from the unique shape and chemical properties of an enzyme's active site
• Cofactors (metal ions, organic molecules) often assist enzymes in catalyzing reactions
• Enzyme classification systems group enzymes based on the types of reactions they catalyze (oxidoreductases, transferases)

Mechanisms of Enzyme Catalysis

• Enzymes lower activation energy for reactions making them energetically favorable
• Induced fit model describes how enzymes change shape to accommodate substrate binding
• Transition state stabilization reduces the energy required for reaction progression
• Covalent catalysis involves the formation of temporary covalent bonds between enzyme and substrate
• Acid-base catalysis utilizes amino acid side chains to donate or accept protons during reactions

Enzyme Kinetics and Regulation

• Michaelis-Menten kinetics describe the relationship between substrate concentration and reaction rate
• Km represents the substrate concentration at half-maximal reaction velocity
• Vmax indicates the maximum reaction velocity achieved at saturating substrate concentrations
• Lineweaver-Burk plots provide a linear representation of enzyme kinetics for easier analysis
• Enzyme inhibitors reduce enzyme activity through competitive, noncompetitive, or uncompetitive mechanisms
• Feedback inhibition regulates metabolic pathways by inhibiting enzymes with pathway end products