Glossary

A regulatory mechanism where ligand binding at one site affects activity at a distant site through conformational changes. Described by MWC (concerted) and KNF (sequential) models.

Insoluble fibrous protein aggregates with a characteristic cross-β sheet structure where β-strands run perpendicular to the fibril axis. Associated with diseases like Alzheimer's and Parkinson's.

A catabolic process where cellular components are sequestered in double-membrane vesicles (autophagosomes) and delivered to lysosomes for degradation and recycling.

A membrane-less compartment formed by liquid-liquid phase separation that concentrates specific proteins and nucleic acids to organize biochemical reactions.

A protein that assists in the folding, unfolding, or assembly of other proteins without being part of the final structure. Examples include Hsp70, Hsp90, and chaperonins like GroEL/ES.

A selective autophagy pathway where proteins bearing a KFERQ-like motif are recognized by Hsc70 and translocated directly across the lysosomal membrane via LAMP2A.

The collection of all thermally accessible conformations a protein can adopt, weighted by their Boltzmann probabilities. Essential for understanding IDPs and dynamic proteins.

A covalent bond between cysteine thiol groups that stabilizes protein structure. Forms in oxidizing environments like the ER; critical for secreted and membrane protein stability.

An amino acid that cannot be synthesized by an organism and must be obtained from the diet. In humans: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.

The attachment of carbohydrate chains to proteins. N-linked glycosylation occurs at asparagine residues; O-linked at serine/threonine. Critical for protein folding, stability, and recognition.

A technique measuring the rate of backbone amide hydrogen exchange with deuterium to probe protein dynamics, folding, and ligand-induced conformational changes.

A protein or protein region that lacks a stable three-dimensional structure under physiological conditions, yet performs essential biological functions through conformational flexibility.

The demixing of a solution into coexisting dense and dilute liquid phases, driven by multivalent interactions. Forms membraneless organelles like stress granules and nucleoli.

An analytical technique that measures mass-to-charge ratios of ions. In proteomics, used for protein identification, sequencing, and PTM characterization via techniques like ESI and MALDI.

A compact, partially folded protein intermediate with native-like secondary structure but lacking fixed tertiary contacts. It represents a kinetic waypoint on the folding pathway.

Large modular enzymes that synthesize peptides independently of ribosomes using an assembly-line logic. Each module incorporates one amino acid, including non-proteinogenic ones.

The rate-limiting formation of initial aggregation seeds (nuclei) from which amyloid fibrils can rapidly elongate. Can be primary (spontaneous) or secondary (fibril-catalyzed).

The covalent amide bond linking amino acids in proteins. Has partial double-bond character due to resonance, restricting rotation and favoring planar trans geometry.

The addition of a phosphate group to serine, threonine, or tyrosine residues by kinases. A reversible modification central to cell signaling and metabolic regulation.

Modular enzymes that synthesize polyketide natural products through iterative Claisen condensations, analogous to fatty acid synthesis but with variable reduction states.

Chemical modifications to proteins after translation, including phosphorylation, acetylation, ubiquitination, and glycosylation. PTMs regulate protein function, localization, and interactions.

A misfolded protein that can induce normal variants of the same protein to adopt the pathological conformation, creating a self-propagating infectious agent without nucleic acids.

A large protein complex (26S) that degrades ubiquitinated proteins. The 20S core has proteolytic activity; 19S regulatory caps recognize substrates and unfold them for degradation.

The arrangement and interaction of multiple protein subunits to form a functional complex. Hemoglobin's α₂β₂ tetramer is a classic example.

A two-dimensional plot of backbone dihedral angles (φ, ψ) showing sterically allowed conformations. Different regions correspond to α-helices, β-sheets, and other structures.

Ribosomally synthesized and Post-translationally modified Peptides. A class of natural products where a ribosomal precursor peptide undergoes extensive enzymatic modifications.

The process by which pre-formed aggregates (seeds) template the misfolding of native proteins, bypassing the lag phase of spontaneous nucleation.

A short, degenerate peptide sequence (3-10 residues) typically found in intrinsically disordered regions that mediates protein-protein interactions and regulatory functions.

A method for chemical peptide synthesis where the growing chain is anchored to an insoluble resin, enabling iterative coupling and deprotection cycles with simple washing steps.

The covalent attachment of ubiquitin to lysine residues via an E1-E2-E3 enzymatic cascade. K48-linked chains target proteins for proteasomal degradation; K63-linked chains regulate signaling.

A molecule with both positive and negative charges at physiological pH. Amino acids exist as zwitterions with protonated amino groups (NH₃⁺) and deprotonated carboxyl groups (COO⁻).