3D Protein Structure: Secondary, Tertiary, and Quaternary

Vocabulary practice flashcards covering secondary, tertiary, and quaternary levels of protein structure, supersecondary motifs, stabilizing noncovalent and covalent interactions, topological folds, and the structure of green fluorescent protein (GFP).

Primary structure

The linear sequence of amino acids linked together in a polypeptide chain.

Secondary structure

The local conformation of a polypeptide backbone, forming regular, repeating arrangements such as $\alpha$-helices and $\beta$-sheets stabilised by backbone hydrogen bonds.

$\alpha$-Helix

A predominantly right-handed helical secondary structure with $3.6$ amino acid residues per turn and a pitch of $5.4\,\text{Å}$, stabilised by hydrogen bonds between backbone $C=O$ groups and $N\text{--}H$ groups situated $4$ residues further along the chain.

Pitch ($\alpha$-helix)

The linear distance that an $\alpha$-helix rises along its central axis per complete turn, measuring $5.4\,\text{Å}$.

Antiparallel $\beta$-sheet

A $\beta$-sheet conformation wherein neighbouring hydrogen-bonded polypeptide strands run in opposite directions ($N\rightarrow C$ alongside $C\leftarrow N$) and can be connected by short loops.

Parallel $\beta$-sheet

A $\beta$-sheet conformation wherein adjacent hydrogen-bonded polypeptide strands run in the same direction, requiring longer crossover connections to link adjacent strands.

Supersecondary motifs

Recurring combinations of secondary structural elements, such as the $\beta\text{--}\alpha\text{--}\beta$ motif, $\beta$-hairpin, $\alpha\text{--}\alpha$ motif, and Greek key motif, which do not constitute a separate level of protein structure.

Greek key motif

A recurring supersecondary structure motif formed by a folded-over $\beta$-hairpin that connects four antiparallel $\beta$-strands.

Protein domain

A compact structural unit within a single polypeptide chain that is often associated with a distinct biological function and typically folds independently of other regions.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

An enzyme containing two distinct functional domains: an N-terminal domain that binds $NAD^+$ and a C-terminal domain that binds glyceraldehyde-3-phosphate.

Tertiary structure

The overall three-dimensional conformation and spatial arrangement of all atoms in a single folded polypeptide chain.

Hydrophobic core

The internal region of a water-soluble globular protein formed by the burial of nonpolar amino acid side chains away from the surrounding aqueous solvent.

Membrane-spanning porin

A channel protein exhibiting an inverted distribution of side chains compared to soluble proteins, having a largely hydrophobic exterior interacting with membrane lipids and a hydrophilic interior lining a central water-filled pore.

Quaternary structure

The spatial arrangement and association of two or more separate polypeptide chains (subunits) into a biologically active, multi-subunit protein complex.

Haemoglobin

A tetrameric oxygen-transport protein exhibiting quaternary structure, composed of four distinct polypeptide chains: two $\alpha$ subunits and two $\beta$ subunits.

Disulphide bond

A covalent cross-link ($-S\text{--}S-$) generated by the oxidation of two cysteine sulfhydryl/thiol ($-SH$) groups, stabilizing tertiary or quaternary protein structures intra- or intermolecularly.

Electrostatic interactions

Ionic attractions that stabilize folded protein structures, formed between oppositely charged side chains such as a carboxylate group ($-COO^-$) of aspartate or glutamate and a protonated amino group ($-NH_3^+$) of lysine.

Van der Waals forces

Weak, short-range noncovalent attractions between uncharged amino acid residues brought into close contact within a folded protein.

Protein topology

The connectivity and specific three-dimensional spatial arrangement of secondary structure elements within a protein fold.

$\alpha/\beta$ barrel

A protein topology formed by alternating $\beta$-strands and $\alpha$-helices arranged such that the $\beta$-strands form a central barrel surrounded on the outside by $\alpha$-helices, as seen in triose phosphate isomerase.

Jelly roll (Swiss roll)

A protein topology formed by rolling up a 4-segment $\beta$-hairpin into a barrel structure, found in proteins such as Peptide-N4-(N-acetyl-$\beta$-D-glucosaminyl) asparagine amidase.

Green Fluorescent Protein (GFP)

A bioluminescent marker protein comprising an 11-stranded $\beta$-barrel that encloses and protects an internal fluorescent chromophore, originally isolated from the jellyfish Aequorea victoria.

GFP chromophore

A light-emitting structure formed by the internal tripeptide sequence Ser–Tyr–Gly through nucleophilic attack of the Ser carbonyl carbon on the Gly amino nitrogen, followed by dehydration and oxidation of the Tyr $C_\alpha\text{--}C_\beta$ bond to yield conjugated double bonds.

Cytochrome $b_{562}$

An Escherichia coli protein classified under the predominant $\alpha$-class, composed of a four-helix bundle fold.

Retinol binding protein

A human transport protein exhibiting an 8-stranded up-and-down $\beta$-barrel topology.