CHE 4341 Ch. 4

Conformation

A spatial arrangement of atoms in a protein that can occur without breaking covalent bonds (e.g., via rotation about single bonds)

Native conformation

The functional, folded state of a protein that is thermodynamically most stable (lowest free energy)

Stability (protein)

The tendency of a protein to maintain its native conformation

Hydrophobic effect

The tendency of nonpolar groups to cluster away from water, driven by an increase in entropy of surrounding water molecules; the major force stabilizing globular protein folding

Solvation layer

The highly ordered shell of water molecules that forms around a hydrophobic or polar molecule in solution

Disulfide bond

A covalent bond between two Cys residues; strong but uncommon, found mainly in extracellular/secreted proteins

Salt bridge (ion pair)

An ionic interaction between oppositely charged amino acid side chains; strength increases in low-dielectric (nonpolar) environments

Van der Waals interactions

Weak dipole-dipole interactions that are individually insignificant but collectively contribute to protein stability in tightly packed regions

Peptide bond (peptide group)

The planar, rigid bond linking amino acids, with partial double-bond character that prevents free rotation

Phi (φ)

Dihedral angle of rotation about the N–Cα bond

Psi (ψ)

Dihedral angle of rotation about the Cα–C bond

Omega (ω)

Dihedral angle of the peptide bond itself (Cα–C–N–Cα); nearly always 180° (trans)

Trans peptide bond

The configuration found in >99.95% of peptide bonds (except those involving Pro), with the two α-carbons on opposite sides

Cis peptide bond

Rare configuration (~6% for Pro) where α-carbons are on the same side; ω = 0°

Secondary structure

The local, regular spatial arrangement of backbone atoms in a segment of polypeptide, defined by φ and ψ

α helix

A right-handed coiled secondary structure with 3.6 residues per turn and a rise of 5.4 Å per turn, stabilized by intrachain hydrogen bonds

β conformation (β strand)

An extended, zigzag secondary structure of the polypeptide backbone

β sheet

A structure formed by two or more β strands arranged side by side and linked by hydrogen bonds

Parallel β sheet

A β sheet in which adjacent strands run in the same N-to-C direction; repeat period ~6.5 Å

Antiparallel β sheet

A β sheet in which adjacent strands run in opposite directions; repeat period ~7.0 Å; more common than parallel

β turn

A structure that reverses the direction of a polypeptide chain, often involving 4 residues and a hydrogen bond between residue 1 and residue 4

Ramachandran plot

A plot of φ vs. ψ angles used to visualize sterically allowed conformations of a polypeptide backbone

Circular dichroism (CD) spectroscopy

A technique measuring differential absorption of left- vs. right-circularly polarized light, used to assess secondary structure content and folding

Tertiary structure

The complete three-dimensional arrangement of all atoms in a single polypeptide chain

Quaternary structure

The arrangement of multiple polypeptide subunits in a multi-subunit protein

Fibrous proteins

Proteins with polypeptide chains arranged in long strands or sheets, usually with a single type of secondary structure (e.g., keratin, collagen, silk)

Globular proteins

Compact, spherical proteins often containing multiple types of secondary structure

Membrane proteins

Proteins with polypeptide chains embedded in hydrophobic lipid membranes

Intrinsically disordered proteins

Proteins or protein segments that lack a stable, folded three-dimensional structure yet can be functional

α-Keratin

A fibrous, structural protein found in hair, nails, wool, and horns; built from coiled-coil α helices

Coiled coil

A structural motif in which two or more α helices wind around each other (as in α-keratin)

Collagen

The most abundant protein in mammals; a fibrous protein providing tensile strength in connective tissue

Collagen triple helix

A left-handed helix of three collagen α chains supertwisted together in a right-handed superhelix; repeating Gly-X-Y sequence

4-Hydroxyproline (4-Hyp)

An amino acid derivative common in collagen that stabilizes the collagen helix (requires vitamin C for synthesis)

Fibroin

The β-sheet-rich structural protein of silk, produced by insects and spiders

Motif (fold)

A recognizable folding pattern involving two or more elements of secondary structure and their connections

Domain

A part of a polypeptide chain that folds stably/independently and may function as a distinct unit

β-α-β loop

A simple motif of two β strands connected via an α helix

β barrel

An elaborate motif in which many β strands twist and coil into a barrel shape

α/β barrel

A motif built from repeated β-α-β loops, forming a stable barrel with parallel β strands and surrounding α helices

Superfamily (protein)

A group of protein families that share a major structural motif and functional similarity despite low sequence similarity

Protein family

A group of proteins with significant similarity in primary and/or tertiary structure and function

Protomer

The repeating structural unit (single subunit or group of subunits) in an oligomeric protein

Oligomer (multimer)

A protein composed of multiple polypeptide subunits

Myoglobin

A small, oxygen-binding globular protein of muscle; the first protein structure solved by x-ray crystallography (Kendrew)

Hemoglobin

The oxygen-binding protein of red blood cells; a tetramer of two α and two β globin subunits, each with a heme group

Heme group

An iron protoporphyrin prosthetic group that binds oxygen in myoglobin and hemoglobin

Proteostasis

The cellular maintenance of a functional protein population through coordinated synthesis, folding, refolding, and degradation

Denaturation

Loss of three-dimensional protein structure sufficient to cause loss of function

Renaturation

The process by which a denatured protein spontaneously refolds into its native, functional conformation

Anfinsen experiment

Classic experiment (ribonuclease A) demonstrating that a protein's amino acid sequence contains all the information needed for it to fold into its native structure

Levinthal's paradox

The observation that proteins fold far too quickly to be sampling all possible conformations randomly, implying folding follows defined pathways

Free-energy funnel

A model depicting protein folding as a narrowing landscape of decreasing free energy toward the native state

Chaperone

A protein that assists other proteins in folding correctly, without specifying the final structure itself

Hsp70

A family of heat shock proteins (~70 kDa) that bind exposed hydrophobic regions of unfolded/partially folded proteins to prevent aggregation

Chaperonin (GroEL/GroES, Hsp60)

Large multisubunit protein complexes that provide an enclosed chamber for proteins to fold, preventing aggregation

Protein disulfide isomerase (PDI)

An enzyme that catalyzes the rearrangement (shuffling) of disulfide bonds during folding

Peptide prolyl cis-trans isomerase (PPI)

An enzyme that catalyzes interconversion of cis and trans isomers of proline peptide bonds

Amyloid

An insoluble, highly ordered, β-sheet-rich protein fiber associated with disease

Amyloidoses

Diseases caused by amyloid fiber formation from misfolded, normally soluble proteins

Prion

An infectious, misfolded protein (PrPSc) that induces normal PrPC protein to adopt its abnormal, disease-causing conformation

Structural biology

The study of the three-dimensional structures of biomolecules using techniques like x-ray crystallography, NMR, and cryo-EM

X-ray crystallography

A technique that determines protein structure by analyzing the diffraction pattern of x-rays passed through a protein crystal

Nuclear magnetic resonance (NMR) spectroscopy

A technique that determines protein structure in solution by measuring distance-dependent interactions between atomic nuclei

Cryo-electron microscopy (cryo-EM)

A technique that determines structures by imaging many individual flash-frozen molecules and computationally combining 2D images into a 3D structure

Protein Data Bank (PDB)

The public archive of experimentally determined three-dimensional biomolecular structures