Protein Structure and Folding

Flashcards covering the hierarchical structure, classification, visualization, and folding of proteins based on lecture notes.

How are covalent bonds formed?

By electron pairs shared between atoms.

Describe non-covalent interactions.

They are weak, but often many of them act together.

What determines the binding of macromolecules?

Molecular complementarity, based on non-covalent interactions.

How are proteins, nucleic acids, and polysaccharides generated?

By polymerization of small subunits.

What determines the properties of amino acids?

Their side chains.

What are the monomeric subunits of proteins?

Amino acids (aa).

How do amino acids bind to each other to form proteins?

Via peptide bonds.

What is a single chain of more than 30 amino acids called?

A polypeptide.

What is the term for the order of amino acids in a polypeptide?

Its amino acid sequence.

What is the 3D shape of a protein called?

Its conformation.

What determines a protein's conformation?

Its amino acid sequence, but it can be changed by interactions with other molecules.

What do different models or diagrams illustrate regarding proteins?

Different aspects of a protein and different levels of detail.

What are the four levels of protein structure?

Primary, secondary, tertiary, and quaternary structure.

What defines the primary structure of a protein?

The amino acid (aa) sequence.

What type of bond connects amino acids to build peptides?

Peptide bonds.

What are the two different ends of a peptide called?

The amino or N-terminus and the carboxyl or C-terminus.

What term describes the fact that a peptide has two different ends?

Directionality.

Which end of a peptide is always shown on the left side in the primary structure?

The N-terminus.

What two main components make up a peptide?

The backbone and the amino acid side chains.

In what units is the mass of proteins expressed?

Daltons (Da) or kilodaltons (kDa).

What is the average mass for an amino acid in a protein?

113 Da.

What is the secondary structure of a polypeptide?

Short segments with a specific spatial arrangement.

What kind of bonds are responsible for stabilizing the secondary structure?

Hydrogen bonds between backbone amino and carbonyl groups.

What are the most important secondary structures?

Alpha helices and beta sheets.

How are alpha helices and beta sheets often connected?

By beta-turns.

On average, what percentage of a polypeptide consists of alpha helices and beta sheets?

60%.

What are parts of a polypeptide called that have no stable shape?

Intrinsically disordered regions or unstructured regions.

Describe the shape of an alpha helix.

It has a spiral-like shape.

How do repeating hydrogen bonds stabilize the alpha helix?

The carbonyl group of an amino acid makes a hydrogen bond to the amino group of the amino acid four positions further in the polypeptide.

How many amino acids make one full turn in an alpha helix?

3.6 amino acids.

How do side chains determine the nature of an alpha helix?

They determine whether an alpha helix is hydrophilic or hydrophobic.

Where are hydrophilic alpha helices typically located in water-soluble proteins?

On the surface of the protein.

What can hydrophobic alpha helices do within a cell?

They can span lipid membranes.

What are beta sheets composed of?

5-8 amino acid long beta strands.

Where do hydrogen bonds form in beta sheets?

Between backbone carbonyl and amino groups on separate beta strands.

What are the two possible orientations of beta strands in a beta sheet?

Parallel or antiparallel.

What does tertiary structure describe?

The overall conformation of one polypeptide.

What interactions mainly determine the tertiary structure?

Hydrophobic interactions between nonpolar side chains, hydrogen bonds between polar side chains and backbone groups, and covalent disulfide bonds between cysteines.

What are structural motifs in the context of tertiary structure?

They consist of two or more secondary structures that have a specific 3-dimensional form.

Give an example of a structural motif.

A coiled-coil motif, where two alpha helices interact with their regularly arranged hydrophobic side chains.

What is a protein domain?

A higher-level organization than a structural motif, with a specific three-dimensional form that can fold autonomously and may contain several structural motifs.

What is a key difference between a domain and a structural motif regarding folding?

Domains can fold autonomously even when separated from the rest of the protein.

How can the structure and function of domains be modified?

For example, by activation through phosphorylation.

What does 'functional domain' refer to?

A particular activity, such as adding a phosphate group to a protein (kinase domain) or binding to DNA (DNA-binding domain).

What are 'extracellular domain,' 'transmembrane domain,' and 'intracellular domain' used for?

To describe the topological context of a protein's parts within or outside the cell membrane.

What describes the quaternary structure of a protein?

The number and position of polypeptide chains (subunits) in a multimeric protein.

What type of interactions primarily hold the subunits of multimeric proteins together?

Non-covalent interactions.

What role can the subunits of multimeric proteins play in biological processes?

They can perform different steps of a biological process.

What stabilizes the overall conformation of a protein (tertiary structure)?

Hydrophobic interactions and hydrogen bonds involving side chains and backbone groups.

What is the primary determinant of a protein's conformation?

Its amino acid sequence (primary structure).

Which levels of protein structure describe the three-dimensional conformation of proteins?

Secondary, tertiary, and quaternary structure.

What are biomolecular condensates?

Accumulations of proteins into high density without defined quaternary structure or a surrounding membrane, forming a liquid 'droplet' via liquid-liquid phase separation.

What kinds of molecules can biomolecular condensates contain?

One or several different proteins, and other molecules like RNA.

What factors contribute to the formation of biomolecular condensates?

Concentration of proteins, pH, ion concentrations, and chemical modifications of the proteins.

How do proteins often bind to each other in biomolecular condensates?

Via multiple parts of the protein (multivalent), often including intrinsically disordered regions (IDR).

Describe the nature of bonds between proteins in biomolecular condensates.

Each bond is weak and transient.

What are two ways proteins can be classified?

According to their conformation or according to their function.

What software is known for predicting protein conformation with great accuracy?

AlphaFold.

What are the four broad structural classes of proteins?

Globular proteins, fibrous proteins, integral membrane proteins, and intrinsically disordered proteins.

Describe globular proteins.

Compact, 'roundish,' and often water soluble.

Describe fibrous proteins.

Elongated, often stiff, and not easily water soluble.

Describe integral membrane proteins.

They have a domain that is embedded in cell or organelle membranes.

Describe intrinsically disordered proteins.

They do not have a fixed conformation but can adopt a specific conformation when bound to other proteins.

What is the function of regulatory proteins?

They control the activity of other proteins, for example, by adding/removing small chemical modifications or by bringing proteins into contact (scaffold proteins).

What is the function of structural proteins?

They organize the cell, for example, by stabilizing or changing its shape and by keeping organelles in place; they are often fibrous proteins.

What is the function of motor proteins?

They move other proteins, vesicles, and organelles along the 'rails' of the cytoskeleton.

What is the function of enzymes?

They catalyze chemical reactions (make and break covalent bonds), for example, to synthesize macromolecules.

What is the function of transport proteins?

They move molecules across membranes, and some carry molecules in the bloodstream.

What is the function of signaling molecules?

They transmit information from the exterior to the interior of cells or within cells.

Can a protein belong to more than one functional class?

Yes, for example, some signaling molecules also have enzymatic activity.

Why is correct protein folding essential?

The function of a protein requires that it is folded into its correct structure.

What is 'denaturation' in the context of proteins?

Destroying a polypeptide's secondary and tertiary structure, for example, by heating, which disrupts noncovalent bonds.

What is 'renaturation' in the context of proteins?

The refolding of a denatured protein into its native state, which some proteins can do in a test tube.

What constrains protein folding regarding peptide bonds?

There is no rotation of peptide bonds (except for proline).

Where does rotation occur in a polypeptide backbone to allow folding?

Only next to the alpha carbon (Calpha).

How do side chains influence protein folding angles?

They influence the angle of the rotation.

What unique effect does proline have on an alpha helix?

It causes a bend in an alpha helix.

What are chaperones?

Proteins that help other proteins to fold correctly.

Why are chaperones important in the cytoplasm?

They reduce or prevent the binding of not fully folded proteins (partially folded) to other molecules, which is a risk in the crowded cytoplasm.

Do chaperones require energy for their function?

Yes.

What is the most important determinant of protein folding?

The primary structure (amino acid sequence).

After folding, which amino acids can interact with each other?

Amino acids that are not adjacent in the primary sequence.