BCH210: Lecture 4

Primary (1˚)

The linear sequence of amino acids encoded by DNA

Secondary (2˚)

Periodic, regular structures (alpha helix, beta strands & turns)

Tertiary (3˚)

Folding of secondary structures into defined protein motifs and domains

Quaternary (4˚)

Assembly of distinct chains into multi-subunit structures

Peptide Bonds

Polar, uncharged bonds that experience resonance, providing characteristics of a double bond

Ramachandran Plot

A plot that maps the allowed regions of phi and psi dihedral angles in protein backbone structures

Phi/Psi Rotation

Is allowed around the bonds linking the amide (phi bond) and carbonyl (psi bond) to the alpha carbon, and 𝜙 and Ѱ angles range from -180˚ to +180˚, but not all angles are permitted

Types of Secondary Structures

the 𝜶 helix and the 𝜷 strand/pleated sheet (which has beta turns to help with linkage)

Alpha Helix

"Intra-strand hydrogen bonds form between backbone residues down the centre of the helix

The C=O from one amino acid hydrogen bonds to an N-H group 4 residues away ( i & i+4)

There are approximately 36 residues per 360˚ turn, and each residue is 15 Å high, creating a compact structure

"

Beta Strand

An extended, zigzag polypeptide chain conformation that interacts laterally with other strands to assemble into beta-pleated sheets

Parallel

A beta-sheet structural alignment where all interacting beta strands run in the exact same direction from N-terminus to C-terminus

Antiparallel

A beta-sheet structural alignment where adjacent beta strands run in alternating, opposite directions, yielding linear and stronger hydrogen bonds

Relative Frequency

Determines whether the amino acid prefers to be in an alpha helix or beta strand, with a frequency of more than 1 indicating that the amino acid prefers to be in that frequency

Coiled Coil

A protein structural motif where two or more alpha helices twist around each other to form a stable rope-like bundle

Helix Bundle

A stable supersecondary structure composed of several tightly packed alpha helices running roughly parallel or antiparallel to each other

BAB Unit

A supersecondary structural motif consisting of an initial beta strand connected by a loop to an alpha helix, followed by a loop to a parallel beta strand

Hairpin Structure

A simple protein or structural loop motif where the polypeptide chain reverses direction sharply through a tight beta turn

Greek Key

A complex supersecondary structural motif formed by four adjacent antiparallel beta strands folded into a specific interlocking topology

Beta-Barrel

A large, closed beta-sheet structure that twists into a toroidal cylinder, where the first strand hydrogen-bonds to the final strand

Multiple-Subunit Proteins

May consist of identical or non-identical polypeptides held together covalently or noncovalently in a quaternary structure with different subunits arising from multiple genes or due to the posttranslational cleavage of precursors

Antibodies

Y-shaped protective immune glycoproteins produced by plasma B cells that bind with high affinity to specific foreign antigens

X-Ray Crystallography

A high-resolution biophysical method that determines the 3D atomic structure of a molecule by analyzing the scattering patterns of X-rays passing through a crystal

Crystal

A homogeneous, geometric solid form made up of highly ordered, symmetrically repeating macromolecular arrangements

X-Ray Diffractometer

An instrument that measures the exact angles and intensities of X-rays scattered or diffracted by a crystalline specimen

Protein Data Bank (PDB)

An international, open-access digital archive that repositories 3D structural data coordinates for biological macromolecules

Nuclear Magnetic Resonance (NMR)

A solution-based biophysical technique that monitors the magnetic states of specific nuclei to elucidate macromolecular structures

1D NMR

A basic one-dimensional NMR spectrum tracking chemical shifts along a single frequency axis to provide a general molecule profile

2D NMR

Advanced multi-dimensional NMR that spreads overlapping signals across two frequency axes, mapping spatial or bond-separated atomic correlations

Cryo-Electron Microscopy (Cryo-EM)

An imaging method where biological specimens are flash-frozen in vitreous ice and viewed with transmission electron microscopy to determine high-resolution 3D structures

Chromophores

Functional groups that contain conjugated double bonds that absorb ultraviolet (UV) and/or visible light at specific wavelengths

Fluorophores

Specialized chemical components or molecules that can absorb light at a short excitation wavelength and re-emit it at a longer wavelength

Tryptophan Fluorescence

An intrinsic fluorescence method monitoring tryptophan emission, which shifts based on local environment polarity, to measure protein folding states

Protein Folding

The physical process by which an unstructured, linear polypeptide folds into its functional, low-energy 3D native conformation

Chaperone Proteins

Specialized folding helper proteins that bind transiently to folding polypeptides to prevent aggregation or misfolding events

Denaturation

The structural unraveling of a protein's secondary, tertiary, and quaternary folds under environmental stress, rendering it inactive

Protein Diseases

Pathological conditions (eg, Alzheimer's, Huntington's) stemming from systemic protein misfolding, aggregation, or amyloid plaque buildup

Prions

Highly infectious, abnormal misfolded protein particles that cause fatal neurodegenerative diseases by inducing normal host proteins to misfold

Native State

The fully folded, thermodynamically stable, and biologically operational three-dimensional conformation of a protein

Beta Turns

A tight, four-residue secondary structure loop that reverses the polypeptide backbone direction, stabilized by a hydrogen bond between residues i and i+3