Chapter 6.1

Protein Structure and Organization

Secondary Structure

Proteins are polymers of amino acids that fold into specific secondary structures, which are stabilized by hydrogen bonds between backbone atoms. The most common secondary structures are the alpha helix and beta sheet.

• Alpha Helix: A right-handed coil where each backbone N-H group forms a hydrogen bond with the C=O group four residues earlier. Typical phi ($\phi$) and psi ($\psi$) angles for alpha helices are approximately $\phi = -60^\circ$, $\psi = -45^\circ$.

• Beta Sheet: Composed of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a sheet-like structure. Beta sheets can be parallel or antiparallel depending on the direction of the polypeptide chains.

• 310 Helix: A less common, tighter helical structure compared to the alpha helix.

Example: The stick and cartoon representations in the notes show the location of helical regions in a protein sequence, highlighting the main-chain atoms and their arrangement.

Tertiary Structure

The tertiary structure refers to the overall three-dimensional folding of a single polypeptide chain, stabilized by interactions among side chains and backbone atoms. This level of structure determines the protein's functional conformation.

• Helical Regions: Interact to define the folded structure, as seen in beta globin and myoglobin.

• Bound Heme Group: Many proteins, such as globins, contain prosthetic groups like heme, which are essential for their biological function (e.g., oxygen transport).

Example: The tertiary structure of beta globin is shown with helical regions and a bound heme group in a space-filling display.

Quaternary Structure

Quaternary structure describes the arrangement and interaction of multiple polypeptide chains (subunits) in a multi-subunit protein complex.

• Subunit Association: Multiple folded polypeptide chains associate to form a functional protein complex.

• Example: Hemoglobin consists of multiple globin chains, each with its own tertiary structure, assembled into a quaternary structure.

Polypeptide Backbone Geometry

Amide Plane and Torsion Angles

The polypeptide backbone consists of repeating amide planes. The conformation of the backbone is defined by two main torsion angles:

• Phi ($\phi$) Angle: Rotation about the N–Cα bond.

• Psi ($\psi$) Angle: Rotation about the Cα–C bond.

These angles determine the secondary structure adopted by the polypeptide chain.

Steric Constraints

Certain combinations of $\phi$ and $\psi$ angles are sterically forbidden due to atomic crowding. For example, $\phi = 0^\circ$ and $\psi = 0^\circ$ result in a sterically nonallowed conformation due to clashes between main-chain atoms.

Parameters of Secondary Structures

Structural Parameters

Secondary structures are characterized by the number of residues per turn, rise per residue, and pitch (distance per turn).

Structure Type	Residues per Turn	Rise (Å) per Residue	Pitch (Å)
Beta strand (antiparallel)	2.0	3.4	6.8
Beta strand (parallel)	2.0	3.2	6.4
Alpha helix	3.6	1.5	5.4
310 helix	3.0	2.0	6.0

Additional info: Table entries inferred from standard protein structure parameters.

Amyloid Formation and Disease

Protein Misfolding and Amyloid Fibrils

Proteins can misfold, leading to the formation of amyloid fibrils, which are associated with various diseases. The process involves local unfolding of destabilized regions, association of unfolded regions, and formation of insoluble amyloid deposits.

• Folded Protein: Native, functional conformation.

• Local Unfolding: Destabilized regions unfold, exposing hydrophobic surfaces.

• Amyloid Fibril Formation: Unfolded regions associate to form beta-sheet-rich fibrils.

• Amyloid Deposits: Accumulation of fibrils leads to tissue damage and disease (e.g., amyloidosis).

Example: Whole-body scan images show amyloid deposits in a patient before and after treatment, illustrating the clinical impact of protein misfolding.

Protein Structure Visualization

Ribbon and Space-Filling Models

Protein structures are often visualized using ribbon diagrams to highlight secondary structure elements and space-filling models to show the location of bound groups (e.g., heme).

• N-terminus and C-terminus: Indicate the start and end of the polypeptide chain.

• Side Chains: Shown as thin lines extending from the backbone.

• Bound Heme Group: Displayed as a space-filling model to emphasize its position within the protein.

Example: The provided image shows a globin protein with labeled termini, side chains, and a bound heme group.

Summary Table: Secondary Structure Torsion Angles

Secondary Structure	Psi ($\psi$) Angle Range	Phi ($\phi$) Angle Range
Beta strand	+120° to +160°	-120° to -160°
Alpha helix	-30° to -60°	-60° to -45°
310 helix	+130° to +160°	-49° to -26°

Additional info: Table entries inferred from standard protein structure parameters.