Protein Structure and Function Review

A set of 100 question-and-answer flashcards covering protein structure, amino acids, bonding, and historical scientific contributions based on the lecture material.

What is the approximate chemical composition of water in a bacterial cell?

$70\%$ of total cell weight

What percentage of the dry weight of a bacterial cell is composed of macromolecules like proteins and nucleic acids?

$$87\%$$

How are proteins defined structurally?

Linear polymers of $\alpha$-amino acids joined by peptide bonds.

In the formation of a peptide bond, which groups condense together?

The $\alpha$ carbonyl group of one amino acid and the $\alpha$ amino group of another.

What is the general formula of an amino acid side chain denoted by?

The $R$ group.

What occurs to the amino and carboxyl groups of an amino acid at $pH\,7$?

Both groups are ionized, forming a zwitterion.

What are the two mirror-image isomers of the $\alpha$-carbon atom called?

$L$ and $D$ isomers.

Proteins consist exclusively of which optical isomer of amino acids?

$L$-amino acids.

What is the standard free-energy change ($\Delta G^0$) for peptide bond formation between glycine and alanine?

$$2.2\,kcal/mol$$

What molecule is removed during the formation of a peptide bond?

Water ($H_2O$)

Identify the terminal end of a polypeptide with a free amino group.

The N-terminus (amino terminus).

Identify the terminal end of a polypeptide with a free carboxyl group?

The C-terminus (carboxyl terminus).

What are the four main groups of the 20 $\alpha$-L-amino acids found in proteins?

Negative, positive, uncharged polar, and nonpolar.

Name the two amino acids with acidic (negative) side chains.

Aspartic acid ($Asp$, or $D$) and Glutamic acid ($Glu$, or $E$).

Name the three amino acids with basic (positive) side chains.

Arginine ($Arg$, or $R$), Lysine ($Lys$, or $K$), and Histidine ($His$, or $H$).

Identify the amino acids with uncharged polar side chains.

Asparagine ($Asn$, or $N$), Glutamine ($Gln$, or $Q$), Serine ($Ser$, or $S$), Threonine ($Thr$, or $T$), and Tyrosine ($Tyr$, or $Y$).

Which amino acids possess a polar $-OH$ group?

Serine, Threonine, and Tyrosine.

Which amino acid is actually an imino acid?

Proline ($Pro$, or $P$)

Which amino acid side chains are available for phosphorylation?

Serine, Threonine, and Tyrosine.

Which amino acid residue is often subject to methylation, acetylation, ubiquitination, and sumoylation?

Lysine ($Lys$, or $K$)

Which amino acids are primarily responsible for conformational stability?

Nonpolar amino acids.

Which nonpolar amino acid can form disulfide bonds?

Cysteine ($Cys$, or $C$)

Which amino acid side chains are available for glycosylation?

Asparagine, Serine, Threonine, and Tyrosine.

Calculate the possible unique sequences for an $8$ amino acid peptide.

$$20^8 = 25,600,000,000$$

The average protein is approximately 300 amino acids long. How many possible sequences exist?

$20^{300}$ (more than the number of atoms in the universe).

Which four amino acids represent over $32\%$ of those found in proteins?

Leucine ($L$), Serine ($S$), Lysine ($K$), and Glutamic acid ($E$).

Why is the peptide bond planar?

The peptide bond is resonance-stabilized.

What type of non-covalent bond is an electrostatic attraction between two fully charged atoms?

Ionic bond.

What is the length of a hydrogen bond in nanometers?

$$0.30\,nm$$

What is the strength of a covalent bond in vacuum?

$90\,kcal/mole$ ($377\,kJ/mole$).

What is the strength of a hydrogen bond in water?

$1\,kcal/mole$ ($4.2\,kJ/mole$).

How are spontaneous transient dipoles formed?

By the fluctuations in the distribution of electrons in atoms or molecules.

What is another name for induced dipole-induced dipole interactions?

London Dispersion Force.

What is the typical distance for the van der Waals radius ($r_0$)?

$$\sim 0.35\,nm$$

What is the hydrophobic effect?

Entropically-driven exclusion of non-polar solutes from aqueous media.

Where are nonpolar side chains typically found in a folded soluble protein?

In the hydrophobic core region.

What happens when a protein undergoes irreversible denaturation?

It becomes insoluble due to aggregation.

How do chaperone proteins assist in protein folding?

They help newly synthesized or incorrectly folded proteins reach their correctly folded state.

What did Christian Anfinsen conclude from his studies on ribonuclease A?

All information required for proper protein folding is contained in the primary structure (amino acid sequence).

What reagent can be used to denature a protein by disrupting non-covalent interactions?

A high concentration of urea.

What is the name for the stepwise protein folding intermediate?

Molten globule.

Who was the 2024 Nobel Prize in Chemistry co-recipient for computational protein design?

David Baker.

Which co-recipients won the 2024 Nobel Prize in Chemistry for protein structure prediction?

Demis Hassabis and John Jumper.

What is the name of the tertiary structure prediction algorithm developed by Hassabis and Jumper?

AlphaFold.

In addition to active sites, what other functional surfaces are formed by protein folding?

Receptor binding sites and protein-protein interaction surfaces.

List the four levels of the hierarchy of protein structure.

Primary, Secondary, Tertiary, and Quaternary structure.

Differentiate between globular and fibrous proteins.

Globular proteins are compact and rounded (e.g., hemoglobin), while fibrous proteins are elongated and thread-like (e.g., collagen).

What are the four common models for representing protein structure?

Backbone model, wire model, ribbon model, and space-filling model.

What are the two major elements of secondary structure?

$\alpha$ helix and $\beta$ sheet.

What percentage of secondary structure do $\alpha$ helices and $\beta$ sheets typically account for?

$$60\%$$

How many amino acid residues are there per turn in an $\alpha$ helix?

$$3.6$$

Where are amino acid side chains directed in an $\alpha$ helix?

They are directed outward.

What stabilizes the $\alpha$ helix structure?

Hydrogen bonds between the amide $NH$ and carbonyl $CO$ groups of the polypeptide backbone.

How many amino acids are typically required for an $\alpha$ helix to traverse a plasma membrane?

$18 - 22$ amino acids.

What is a $\beta$ sheet composed of?

$\beta$ strands arranged in parallel or anti-parallel orientation.

What is the secondary structure of Green Fluorescent Protein ($GFP$)?

A $\beta$ barrel.

Who is known as the Father of Structural Biochemistry and proposed the $\alpha$ helix and $\beta$ sheet?

Linus Pauling.

Which two Nobel Prizes did Linus Pauling receive?

Chemistry ($1954$) and Peace ($1963$).

Describe a coiled-coil structure.

Two $\alpha$ helices wound together stabilized by hydrophobic interactions between non-polar side chains.

What is the conserved sequence pattern in a coiled-coil?

A heptad sequence.

What is a 'Leucine Zipper'?

A coiled-coil dimerization domain commonly found in DNA binding proteins like c-Jun.

What is a protein domain?

A stable region of a protein made of secondary structural elements that can fold independently.

When do secondary structures and domains typically begin to fold?

As the nascent polypeptide emerges from the ribosome.

What are protein modules?

Domains that appear in many different proteins, often recombined during evolution for new functionality.

What is the structural composition of an IgG immunoglobulin molecule?

Two heavy chains and two light chains held together by disulfide bonds.

Describe the quaternary structure of Hemoglobin.

A heterotetrameric complex composed of two $\alpha$ subunits and two $\beta$ subunits ($\alpha_2\beta_2$).

What type of complex does the enzyme Neuraminidase form?

A homotetrameric protein complex.

Name three shapes that globular proteins can assemble into.

Dimers, rings, and helices.

Which protein subunits assemble spontaneously into filaments in the presence of ATP?

Globular actin subunits.

What is the structure of the Tobacco Mosaic Virus ($TMV$)?

A helical virus consisting of $2130$ protein subunits ($158$ amino acids each) and an $RNA$ genome.

What is the dimension of the triple helix in a collagen molecule?

$$300\,nm \times 1.5\,nm$$

How are elastin molecules held together in elastic fibers?

By covalent cross-links.

What environment typically favors the formation of disulfide bridges to stabilize proteins?

Extracellular environments (via oxidation).

Which enzyme catalyzes the reduction of disulfide bonds back to cysteine sulfhydryl groups?

This occurs during reduction reactions, often internally in the cell.

What determines the final geometry of the neuraminidase tetramer?

Interaction between the blue and orange binding domains.

How many residues are in the heptad sequence of a coiled-coil?

$$7$$

What is the effect of aggregation on denatured proteins?

It leads to insolubility.

What is the term for a protein consisting of two identical subunits?

Homodimer.

What is the term for a protein consisting of two different subunits?

Heterodimer.

What defines the primary structure of a protein?

The specific amino acid sequence.

What is the typical length of a van der Waals attraction per atom?

$$0.35\,nm$$

Which model of protein representation is best for viewing water-accessible surfaces?

Space-filling or surface models.

Which amino acids are typically excluded from the interior of a globular protein?

Polar/charged amino acids (unless they are involved in bonding/function).

What does 'amphipathic' character mean in the context of an $\alpha$ helix?

The helix has one hydrophobic face and one hydrophilic face.

What is the length of TMV?

$$300\,nm$$

What is the strength of an ionic bond in vacuum compared to water?

$80\,kcal/mole$ in vacuum and $3\,kcal/mole$ in water.

What binds to the loops in the variable domain of an IgG light chain?

Antigens.

In an antic-parallel $\beta$ sheet, how do the strands run?

In opposite N-to-C directions.

In a parallel $\beta$ sheet, how do the strands run?

In the same N-to-C direction.

What prevents the peptide bond from rotating?

Its partial double-bond character due to resonance.

What are the bond angles that define the rotation of the polypeptide backbone?

Phi ($\phi$) and Psi ($\psi$).

Which side chains are most critical for the formation of a protein's hydrophobic core?

Nonpolar side chains like Leucine, Valine, and Phenylalanine.

How many subunits make up the Tobacco Mosaic Virus?

$$2130$$

What provides the information required for a protein to reach its lowest energy natively folded state?

The primary amino acid sequence.

Name a fibrous protein discussed that acts as a carrier protein.

$HPr$ (though Slide 58 lists it as globular, collagen is the major fibrous example).

How do disulfide bonds contribute to protein structure?

They provide covalent stabilization to the tertiary or quaternary structure, especially in extracellular proteins.

What is the result of the oxidation of two cysteine side chains?

The formation of an intrachain or interchain disulfide bond.

Which property of the peptide bond backbone allows it to form hydrogen bonds?

The presence of the $-C=O$ carbonyl and $-NH$ amide groups.

Name a specific protein module mentioned in the transcript.

The $SH2$ domain (Src homology 2).

Who proposed the structure of DNA but 'got the details wrong' according to the notes?

Linus Pauling.