MODULE 3: Chapter 4.2 Flashcards
What determines protein structure and function?
The amino acid sequence
The chemical properties of the amino acid side chains contribute to the protein’s fold and function.
What types of interactions stabilize the structure of folded proteins?
Weak noncovalent interactions
These include hydrogen bonding, van der Waals forces, ionic interactions, and hydrophobic effects.
What is an advantage of weak interactions in biological systems?
They permit flexibility
Proteins can change shape by breaking and re-forming weak interactions.
True or False: Proteins are rigid, crystalline-like structures.
False
Proteins are flexible and undergo conformational changes.
What is the primary (1°) structure of a protein?
The amino acid sequence
It determines how the polypeptide backbone folds into a stable three-dimensional structure.
What is the secondary (2°) structure of a protein?
The regular repetitive arrangement of local regions of the polypeptide backbone
Major secondary structures include β strands, α helices, and β turns.
What are the three major secondary structures in proteins?
- α helices
- β strands
- β turns
These are stabilized by hydrogen bonding and geometry.
What is the tertiary (3°) structure of a protein?
The spatial location of all the atoms in the polypeptide chain
This includes the path of the polypeptide and the positions of the side chains.
What defines the quaternary (4°) structure of a protein?
The organization of multiple polypeptide chains in a protein complex
This can involve multiple copies of the same polypeptide or different polypeptides.
What is a characteristic of the α helix structure?
It is a right-handed helix
The α helix is stabilized by intrastrand hydrogen bonds.
How many residues per turn does an α helix typically have?
3.6 residues
Each residue corresponds to a 100° turn of the helix.
What role does proline play in the α helix structure?
Proline disrupts hydrogen bonding
It lacks a hydrogen on its nitrogen and has a rigid ring structure.
Who first predicted the structure of the α helix?
Linus Pauling and Robert Corey
Their model was validated by the structure of whale myoglobin determined by John Kendrew.
What creates a dipole moment in a peptide bond?
The separation of charge between the carbonyl oxygen and the amide nitrogen
This dipole moment contributes to the overall dipole moment in α helices.
What can be found at the termini of α helices to stabilize them?
Compensating charged amino acids
Negatively charged residues at the N-terminal end and positively charged residues at the C-terminal end.
Fill in the blank: The three major types of secondary structure in proteins are _______.
[α helices, β strands, β turns]
What can neutralize the charge on protein surfaces?
Interactions with H2O or charged ions such as phosphate or Mg2⁺
What is the dipole moment in α helices?
A partial positive charge on the N-terminal end and a partial negative charge on the C-terminal end
What does it mean for an α helix to be amphipathic?
One side of the helix is hydrophobic and the other side is hydrophilic
How is an amphipathic α helix generated?
When amino acids with hydrophilic or hydrophobic properties are positioned every three to four residues along the polypeptide backbone
What is the sequence of residues in an amphipathic α helix from phosphofructokinase-1?
Hydrophilic: Thr145, Glu148, Asp151, Arg153, Arg155, Asp156, Thr157; Hydrophobic: Val146, Val147, Ala149, Ile150, Leu154
What tool can be used to predict the existence of an amphipathic α helix?
A helical wheel representation
Describe the arrangement of hydrophobic and hydrophilic residues in apolipoproteins.
Hydrophobic residues oriented inward, hydrophilic residues facing outward
Describe the arrangement of hydrophobic and hydrophilic residues in rhodopsin.
Hydrophobic residues pointing outward toward the lipid membrane, hydrophilic residues facing inward
What is a β strand?
An extended polypeptide chain with amino acid side chains positioned above and below the backbone
How are β strands depicted in protein models?
As arrows with the arrowhead pointing toward the carboxyl terminus
What is the distance between adjacent amino acids in β strands?
3.4 Å
What stabilizes β sheets?
Hydrogen bonding between backbone NH and CO groups on separate strands
What are the two types of β sheets?
Parallel β sheets and antiparallel β sheets
Which type of β sheet is more stable, parallel or antiparallel?
Antiparallel β sheets
What do β sheets resemble?
Pleated fabric
Why are β sheets usually twisted?
To reduce steric hindrance between amino acid side chains
What are β turns?
Common types of turns connecting two β strands in an antiparallel β sheet
What are the two common types of β turns?
Type I and Type II
What amino acid is often found in β turns and why?
Glycine, because its side chain allows for unusual dihedral angles
What is the typical length range for loops in proteins?
6 to 20 residues
What role do loops play in proteins?
Connect elements of secondary structure and contribute to protein–protein interactions
What does the Ramachandran plot illustrate?
The limitations of φ and ψ angles for amino acids in secondary structures
What secondary structures fall within the allowable ranges of φ and ψ angles?
α helices, β sheets (parallel and antiparallel), β turns
Why are major elements of secondary structures common in proteins?
They minimize steric hindrance and maximize hydrogen bonding
What do the φ and ψ angles of proteins indicate?
They indicate the conformation of amino acid residues in proteins as determined by the Ramachandran plot.
What are the major elements of secondary structures in proteins?
They are α helices, β sheets (parallel and antiparallel), and β turns (type I and type II).
Why are certain φ and ψ angles favored in secondary structures?
They minimize steric hindrance and maximize hydrogen bonds between CO and NH groups.
Which amino acid is commonly found in β turns?
Glycine.
Which amino acid is rarely found in α helices or β sheets?
Proline.
What do values above 1.0 indicate in amino acid propensity for secondary structures?
They indicate a preference for that class of secondary structure.
What are the four general classes of protein structures identified in the PDB?
- Predominantly α helix
- Predominantly β sheet
- α/β combined
- α + β
Define a structural domain in proteins.
An independent folding module within the polypeptide chain.
What is the TIM barrel fold?
An alternating α-helix/β-strand fold, also called an α/β barrel.
What is the Greek key fold?
A protein fold consisting of four or more β strands linked together.
What structural components make up the FERM domain fold?
- FA
- FB
- FC
What does the SCOP system do?
It organizes protein folds into superfamilies, families, and domains.
True or False: The Rossmann fold is commonly found in dehydrogenase enzymes.
True.
Fill in the blank: An average-length protein has approximately ______ amino acids.
300.
What is the significance of analyzing large numbers of protein structures?
It helps identify common themes among protein structures and their functions.
What are motifs in protein structures?
Smaller defined structural units within recognizable protein folds.
What type of structure does the heme binding domain of cytochrome b represent?
A four-helix bundle.
What is the primary function of the FERM domain fold?
To anchor proteins to the cytoplasmic face of the plasma membrane.
What does the topology of the Rossmann fold consist of?
Two regions of alternating α helices and β strands.
What is the TIM barrel fold first identified in?
The glycolytic enzyme triose phosphate isomerase.
What is the purpose of the Protein Data Bank (PDB)?
To provide a web-based archive of atomic coordinates of protein structures.
What is the average number of discrete α helices and β strands in an average-length protein?
Approximately 10 discrete α helices and 10 discrete β strands.
What is the function of the FERM domain fold?
Binds to membrane-associated proteins or glycolipids and anchors proteins to the cytoplasmic face of the plasma membrane.
Which two proteins have similar FERM domain folds despite less than 30% amino acid sequence identity?
Ezrin and Band 4.1.
What evidence demonstrates that missense nucleotide mutations can occur without altering protein structure?
The conserved structure of the FERM domain folds in ezrin and Band 4.1 proteins.
What are the main types of interactions that stabilize tertiary structures in proteins?
Weak interactions, covalent disulfide bonds, and coordinated metal ions.
How are disulfide bonds formed?
When two nearby cysteine residues are oxidized, resulting in a disulfide bridge.
Which neurotoxin contains four disulfide bridges?
Brazilian scorpion TS1 neurotoxin.
What are the two most common metal ions found in proteins?
Iron and zinc.
What is a zinc finger?
A tertiary structure in DNA binding proteins that contains four coordination sites through two cysteine and two histidine residues.
What is quaternary structure in proteins?
The arrangement of multiple polypeptide chains within protein complexes.
What is a homodimer?
An oligomer consisting of two identical protein subunits.
What is the simplest type of quaternary structure?
Homodimer.
List three ways quaternary structures provide increased functionality to proteins.
- Structural properties not present in individual subunits
- Regulation of protein function through conformational changes
- Increased efficiency of biochemical processes by bringing functional components together.
What is keratin?
A fibrous protein that consists of coiled coil dimers linked by disulfide bridges.
What is the role of disulfide bridges in keratin?
They provide strength through covalent cross-linking between coiled coil dimers.
What type of protein is silk fibroin?
A fibrous protein consisting of multiple protein subunits with a repeating secondary structure of β sheets.
What is the repeating tripeptide sequence commonly found in collagen?
Gly-X-Y, where X is usually Pro and Y is often 4-hydroxyproline.
How does collagen stabilize its triple helix structure?
Through hydrogen bonds and interstrand hydrophobic interactions.
What vitamin is essential for the hydroxylation of proline in collagen synthesis?
Vitamin C (ascorbate).
What condition can arise from a deficiency in vitamin C?
Scurvy.
True or False: Collagen has an α-helix structure.
False.
What is the primary function of collagen?
To provide structural support in connective tissues.
How many subunits does silk fibroin from Bombyx mori consist of?
Three protein subunits.
What type of protein complex is collagen?
A protein complex that forms a biological fiber.
What is the characteristic structure of a keratin subunit?
A coiled coil consisting of two helical polypeptides.
Fill in the blank: The amino acid sequence of fibroin heavy chain contains stretches of _______ residues.
Polyalanine.
What type of interactions stabilize the collagen triple helix?
Hydrogen bonds and hydrophobic interactions.
What is the structural arrangement of collagen?
Three intertwined left-handed helices forming a right-handed triple helix.
What is the biochemical significance of 4HyP in collagen?
4HyP is required to form strong noncovalent interactions within the collagen helix.
What condition can arise from a diet deficient in vitamin C?
Scurvy.
Who conducted one of the first controlled clinical trials for scurvy in 1747?
Dr. James Lind.
What dietary source helped British sailors recover from scurvy?
Citrus fruits.
What are two rich sources of vitamin C?
- Citrus fruits
- Potatoes
What enzyme converts proline to hydroxyproline using vitamin C?
Prolyl hydroxylase.
What shape do multi-subunit globular proteins often take?
Somewhat spherical shapes.
What is the structure of the bacteriophage φ29 DNA packaging motor?
It consists of 12 identical α subunits forming a concentric α12 homododecamer complex.
What is the function of the bacteriophage φ29 DNA packaging motor?
Guides newly replicated DNA into the viral capsid prior to cell lysis.
What are the components of the heterotrimeric G protein complex?
- α subunit
- β subunit
- γ subunit
What does the G protein complex dissociate into upon activation?
- Gα subunit
- Gβγ heterodimer
What is the composition of the hemoglobin protein complex?
It contains two copies each of an α and a β protein subunit, forming an α2β2 heterotetramer.
What type of proteins are immunoglobulins also known as?
Antibodies.
What is the composition of an immunoglobulin protein complex?
Two heavy-chain subunits (H) and two light-chain subunits (L) forming an H2L2 heterotetramer.
What is the biological function of antibodies?
To bind foreign molecules called antigens.
What is released from antibodies when treated with proteases like papain?
- Antigen binding fragment (Fab)
- Crystallization fragment (Fc)
What is the immunoglobulin fold?
An all-β structure consisting of two β sheets forming a two-layered sandwich with a Greek key fold.
What describes the primary structure of proteins?
The amino acid sequence.
What are the common types of protein secondary structures?
- α helix
- β strand
- β turn
What is the definition of tertiary structure in proteins?
The spatial location of all the atoms in a polypeptide chain.
What is the definition of quaternary structure in proteins?
The structure of a protein complex containing more than one polypeptide chain.
What is a motif in protein structure?
A small but distinct structural unit of a protein fold.
What is a coiled coil in protein structure?
Two helical polypeptides that are wrapped around each other.
What is the condition caused by vitamin C deficiency?
Scurvy.
What is the role of the variable domain in immunoglobulin subunits?
It binds to antigen molecules.
What is the role of the constant domain in immunoglobulin subunits?
It provides structural stability.
What are the two types of β sheets?
- Parallel β sheet
- Antiparallel β sheet
What is a Rossmann fold?
A structural motif characterized by alternating α helices and β strands.
What is the TIM barrel fold?
An alternating α-helix/β-strand fold first identified in triose phosphate isomerase.
What do Ramachandran diagrams illustrate?
The allowed conformations of amino acids in a protein structure.
