Biochemistry: Protein Structure, Folding, and Function

Comprehensive vocabulary flashcards covering noncovalent interactions, amino acid properties, secondary and tertiary protein structures, folding energetics, chaperones, and protein degradation pathways based on Lectures 1 through 5.

Hydrogen Bond Donor

A chemical group consisting of a hydrogen atom covalently bonded to an electronegative atom that can be shared with an electronegative acceptor atom.

Hydrogen Bond Acceptor

An electronegative atom bearing an available lone pair of electrons that attracts and interacts with an electropositive hydrogen atom.

Ion-Dipole Interaction

A noncovalent electrostatic interaction between a fully charged ion and a polar molecule, such as the hydration shell formed around a sodium ion by water molecules.

Size Exclusion Chromatography

A column chromatography technique (gel filtration) that separates proteins based on molecular size, where larger proteins travel faster and elute first because they are excluded from the internal pore volume of the resin.

Ion Exchange Chromatography

A separation method based on net charge; in cation exchange chromatography, negatively charged molecules elute first while positively charged molecules bind to the resin.

Affinity Chromatography

A purification technique that separates molecules based on highly specific, reversible biological binding interactions between the target protein and an immobilized ligand.

Peptide Bond

A rigid, planar covalent bond between the carbonyl carbon of one amino acid and the alpha-amino nitrogen of the next; due to partial double-bond character, it cannot rotate.

Phi ($\phi$) Angle

The dihedral torsion angle of rotation around the single bond between the nitrogen atom and the alpha-carbon ($\text{C}_\alpha$) of the polypeptide backbone.

Psi ($\psi$) Angle

The dihedral torsion angle of rotation around the single bond between the alpha-carbon ($\text{C}_\alpha$) and the carbonyl carbon atom of the polypeptide backbone.

Proline

A cyclic nonpolar amino acid whose side chain loops back to its backbone amino group; it possesses the most constrained $\phi$ and $\psi$ angles and acts as a helix breaker because it lacks a backbone $\text{N}-\text{H}$ donor for hydrogen bonding.

Glycine

The smallest, nonpolar amino acid with a single hydrogen atom as its side chain; it is the only achiral standard amino acid and is exceptionally flexible, which disfavors alpha-helix formation.

Alpha Helix

A right-handed coiled secondary structure stabilized primarily by hydrogen bonds within the backbone between residue $n$ and residue $n+4$, exhibiting a rise of $1.5\,\text{\AA}$ per residue.

Alpha Helix Dipole

The macroscopic electric dipole generated across an alpha helix due to the alignment of individual peptide bond dipoles, resulting in a partial positive charge ($\delta+$) at the N-terminus and a partial negative charge ($\delta-$) at the C-terminus.

Parallel Beta Sheet

A beta sheet conformation where adjacent polypeptide strands run in the same direction, held together by slanted (sideways) inter-strand backbone hydrogen bonds that provide less stability than antiparallel arrangements.

Antiparallel Beta Sheet

A beta sheet conformation where adjacent polypeptide strands run in opposite directions, held together by straight, linear inter-strand backbone hydrogen bonds that confer greater structural stability.

Four-Helix Bundle

An all-alpha ($\alpha$) tertiary fold (such as in Cytochrome b562) formed by amphipathic alpha helices whose hydrophilic faces face outward toward water while hydrophobic faces pack tightly inward.

EF Hand

A helix-loop-helix ($\alpha$) motif where the connecting loop is enriched in negatively charged (acidic) and oxygen-containing amino acids whose side chains coordinate binding to $\text{Ca}^{2+}$.

Beta Barrel

A beta-sheet ($\beta$) tertiary structure that closes onto itself like a barrel; commonly enriched with nonpolar residues on the inside to bind small hydrophobic ligands (e.g., retinol) and polar residues on the solvent-exposed exterior.

Beta Propeller

An all-beta ($\beta$) tertiary structure composed of repeating blade-like motifs arranged radially, where surface loops at one face frequently form ligand-binding or catalytic active sites.

Horseshoe Fold

An alternating $\alpha/\beta$ tertiary fold connected by loops that is enriched in Leucine residues; the hydrophobic packing of Leucine side chains stabilizes the curved interior surface.

TIM Barrel

A conserved alternating $\alpha/\beta$ domain fold consisting of eight parallel beta strands surrounded by eight alpha helices, widely utilized as an enzymatic structural core.

Rossmann Fold

An $\alpha\beta$ alternating structural motif common in nucleotide-binding proteins whose primary physiological ligand is $\text{NAD}^+/\text{NADH}$.

SH2 Domain

An $\alpha+\beta$ structural domain that specifically functions to recognize and bind phosphotyrosine ($\text{pY}$) motifs on client proteins.

Quaternary Structure

A multi-subunit structural assembly consisting of two or more separate tertiary polypeptide chains joined by noncovalent interactions and occasionally disulfide bonds (e.g., hemoglobin, collagen).

Heptad Repeat

A repeating seven-residue motif ($\text{abcdefg}$) characteristic of coiled-coils, where positions $a$ and $d$ form the internal hydrophobic core, $e$ and $g$ participate in ionic pairs, and $b$, $c$, and $f$ remain solvent-exposed.

Leucine Zipper

A specialized coiled-coil motif found in DNA-binding proteins characterized by an enrichment of Leucine at the $d$ positions of the heptad repeat to mediate hydrophobic dimer packing.

Collagen Triple Helix

A unique structural superhelix formed by three polypeptide chains with a repeating $\text{Gly-X-Y}$ sequence, stabilized by inter-chain hydrogen bonds, small Glycine residues packed into the tight center, and Proline/hydroxyproline providing structural rigidity.

Fibroin

The primary structural protein of silk, deriving its extreme stability and tensile strength from tightly packed beta-sheet crystallites, and its flexibility from interspersed amorphous regions.

Anfinsen's Experiment

A landmark series of denaturation and refolding experiments on ribonuclease demonstrating that a protein's primary amino acid sequence contains all necessary information to direct native three-dimensional folding.

Levinthal's Paradox

The observation that because a polypeptide chain possesses an astronomical number of possible conformations, proteins cannot reach their biologically active native fold through random sampling.

Molten Globule

A dynamic protein folding intermediate that has formed substantial native secondary structure ($2^\circ$) but lacks packed tertiary structure ($3^\circ$), rendering it sticky and highly prone to aggregation.

Folding Funnel

A conceptual thermodynamic model where funnel width represents conformational entropy/free energy states and funnel height corresponds to folding progress/free energy ($\Delta G$).

GroEL/GroES (HSP60/HSP10)

A multi-subunit molecular chaperone system wherein GroEL forms a cylindrical barrel and GroES acts as a detachable lid to encapsulate partially folded intermediates in an isolated chamber for folding.

GroEL Apical Domain

The flexible rim domain of the GroEL barrel lined with exposed hydrophobic residues that functions to bind unfolded client proteins and recruit the GroES cap.

GroEL Equatorial Domain

The structural base domain of GroEL that binds and hydrolyzes ATP, provides inter-ring stability, and transmits allosteric signals during the chaperonin cycle.

HSP100

An ATP-driven disaggregase chaperone forming a hexameric ring with a narrow central pore through which it threads and unfolds aggregated proteins to give them an opportunity to refold.

HSP70

A molecular chaperone consisting of a nucleotide-binding domain and a substrate-binding domain with a lid; client peptides bind when ADP is bound and are released when ATP binds and opens the lid.

26S Proteasome

A large ATP-dependent multi-catalytic protease consisting of a 19S cap that binds, deubiquitinates, and unfolds targets, and a 20S core cylinder that cleaves peptide bonds to degrade polyubiquitinated proteins.

Ubiquitin

A small regulatory protein attached via an isopeptide bond to the lysine side chains of misfolded or short-lived proteins through an E1, E2, and E3 enzymatic cascade to target them for proteasomal degradation.

Protein Disulfide Isomerase (PDI)

An endoplasmic reticulum enzyme that catalyzes disulfide exchange; oxidized PDI contains a disulfide bond and introduces new crosslinks into clients, while reduced PDI possesses two free thiol groups ($-\text{SH}$) to correct and rearrange mismatched disulfide bonds.

Prion ($\text{PrP}^{\text{Sc}}$)

An infectious misfolded conformer that acts as an epigenetic template forcing natively folded cellular prion proteins ($\text{PrP}^\text{C}$) to adopt the pathogenic conformation without requiring any nucleic acid genome.

Amyloid-Beta ($\text{A}\beta$)

A peptide whose pathological fibril assembly is mediated by hydrophobic side-chain interactions, particularly involving Phenylalanine (Phe/F), forming sticky self-associating interfaces.