Protein Functions (DHL-2022)

Protein function is limited and defined by protein structure

• Core idea: A protein’s function is constrained and determined by its three‑dimensional structure. Without the right structure, a protein cannot perform its role effectively.

Learning objectives

• At the end of this video, you will be able to:

  • Identify several classes of proteins based on their function.

  • Recognize representative examples for each functional class.

  • Understand how structure informs function and how conformational changes enable activity.

Catalysts (enzymes)

• Definition and role

  • Catalysts are proteins that make chemical reactions faster by lowering the activation energy needed for the reaction to proceed.

  • They do this by stabilizing the transition state, properly orienting substrates, and creating a favorable microenvironment.

• Key mechanism concepts

  • Active site geometry and substrate binding are optimized to reduce the energy barrier.

  • Conformational changes can bring substrates together or exclude water, facilitating reaction steps.

  • Induced fit: the enzyme may shift shape upon substrate binding to achieve optimal catalysis.

• Examples from the slides

  • Citrate Synthase: shown in open conformation and closed conformation, illustrating how structural changes regulate substrate access and catalysis.

  • Why it matters: the enzyme participates in the citric acid cycle by forming citrate from acetyl‑CoA and oxaloacetate; the open→closed transition is a textbook example of induced fit and allosteric-like conformational control.

• Significance

  • Enzymes are central to metabolism, drug design, and biotechnology.

  • Structure–function relationships in enzymes underpin how inhibitors or activators alter activity.

Structural proteins

• Definition and role

  • Structural proteins provide support and shape to cells and tissues; they form frameworks and mechanical integrity.

• Examples

  • Actin filament: a cytoskeletal filament made of G‑actin monomers organized into F‑actin filaments.

• Significance

  • Shape maintenance, cell movement, and mechanical resilience depend on these scaffolds (cytoskeleton).

  • Abnormalities in structural proteins can lead to disease phenotypes (e.g., muscular dystrophies, filament misassembly).

Transporters

• Definition and role

  • Transporters carry other molecules around the cell or across membranes; they can be channels or carriers that selectively move substances.

• Example

  • Aquaporin: a water channel that facilitates rapid and selective water transport across membranes.

• Significance

  • Regulation of cellular hydration, solute gradients, and overall cellular homeostasis.

  • Mutations or malfunctions can disrupt water balance and solute transport, impacting physiology.

Motor proteins

• Definition and role

  • Motor proteins generate movement either within cells (intracellular transport) or to move the cell itself.

• Mechanism overview

  • They convert chemical energy from ATP hydrolysis into mechanical work (power strokes) to move along cytoskeletal tracks.

• Example

  • Myosin attached to actin: a classic interaction where myosin's conformational changes drive muscle contraction and other cellular movements.

• Significance

  • Essential for muscle contraction, vesicle transport, cell division, and organelle positioning.

Storage proteins

• Definition and role

  • Storage proteins store other molecules until they are needed by the organism.

• Example

  • Serum albumin carrying fatty acids: serves as a carrier protein for hydrophobic molecules in the bloodstream.

• Significance

  • Enables transport and availability of nutrients; maintains osmotic balance and reservoir for essential molecules.

Signalers (signaling molecules)

• Definition and role

  • Signalers carry signals from one cell to another, initiating cellular responses.

• Example

  • Insulin: a peptide hormone that signals transcriptional and metabolic changes in target cells.

• Significance

  • Coordination of growth, metabolism, and homeostasis; dysregulation linked to diseases like diabetes mellitus.

Receptors

• Definition and role

  • Receptors receive signals and transmit them across cellular membranes or into the cell, triggering downstream pathways.

• Example

  • G‑protein coupled receptor (GPCR): a large and diverse family that transduces extracellular signals via G proteins.

• Significance

  • Central to sensory perception, neurobiology, and pharmacology; many drugs target GPCRs.

Regulators

• Definition and role

  • Regulators turn other proteins or cellular functions on and off, enabling control and timing of cellular processes.

• Example

  • TATA Binding Protein (TBP) bound to DNA: a transcription factor that helps initiate transcription by recruiting RNA polymerase II and other factors.

• Significance

  • Precise control of gene expression; regulated transcription is fundamental to development, differentiation, and response to environmental cues.

Unique proteins

• Definition and role

  • Some proteins do not fit easily into any single predefined category; they can have distinctive or multifaceted functions.

• Example

  • Green Fluorescent Protein (GFP): used widely as a fluorescent tag to visualize cellular processes in living cells.

• Significance

  • GFP-inspired tools revolutionized cell biology, enabling live imaging, gene expression studies, and reporter assays.

Take care to distinguish examples from categories

• Important caveat

  • Do not confuse the example with the category: a single protein may participate in multiple functional roles or be studied within a specific illustrative example that does not exhaust its entire functional repertoire.

  • The slides emphasize looking at representative examples while understanding the broader functional category.

Connections to broader context and implications

• Connections to foundational principles

  • Structure determines function across all protein classes; conformational dynamics enable regulation and activity.

  • The same structural framework can support diverse roles (e.g., a single scaffold can bind ligands, transmit signals, or act as a channel depending on context).

• Real-world relevance

  • Enzyme mechanisms inform drug design (inhibitors, activators).

  • Transporters and receptors are primary drug targets; understanding their structure guides therapeutic development.

  • Visual resources (PDB structures) support structure-based design and education.

• Ethical, philosophical, or practical implications

  • Use of structural data (PDB) in drug discovery raises ethical questions about access, cost, and global health equity.

  • Advances in protein engineering (e.g., GFP derivatives) raise considerations about biosafety and dual-use research.

  • Education and communication benefits from clear distinctions between an example and a category to avoid misconceptions in students and researchers.