Protein: Structure + Function (lec 14 not on midterm 2) Flashcards

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1
Q

(T/F) Human genome has around 20k to 23k protein encoding genes that through alternative splicing of mRNAs and post-translational modifications generate hundreds of thousands of distinct protein activity.

A

True!

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2
Q

What are proteins?

A

Polymers composed of the 20 amino acids with different R group side chains.

Amino acid side chains determine the distinct properties of individual proteins.

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3
Q

Match the following protein structures to their definition:

1) Primary
2) Secondary
3) Tertiary
4) Quaternary
5) Supramolecular complexes

A) large-scale assembly - consisting of tens to hundreds of subunits and other biopolymers such as nucleic acids (big power house engines; RIBOSOME)

B) association between multipeptide complexes (multimeric structure)

C) local folding of the chain into alpha helices and b sheets with lots of H-bonds.

D) overall 3D conformation - composed of 2° structural elements and loops + turns. May form distinct, independently stable domain.

E) linear sequence of amino acids linked by peptide bonds

A

Primary: linear sequence of amino acids linked by peptide bonds

Secondary: local folding of the chain into alpha helices and b sheets with lots of H-bonds.

Tertiary: overall 3D conformation - composed of 2° structural elements and loops + turns. May form distinct, independently stable domain.

Quaternary: association between multipeptide complexes (multimeric structure)

Supramolecular: large-scale assembly - consisting of tens to hundreds of subunits and other biopolymers such as nucleic acids (big power house engines; RIBOSOME)

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4
Q

What does protein function depend on?

A

Specific binding interactions and conformation changes in the structure of a properly folded protein

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5
Q

What are the 6 main functions of proteins? Briefly describe them.

A

1) Structure - they organize the genome, organelles, cytoplasm, protein complexes, and membranes in 3D space

2) Regulation - control protein activity (e.g. post translation modification)

3) Signalling - monitoring the environment and transmitting information

4) Transport - moving small molecules and ions across membranes

5) Enzyme activity - catalyzing chemical reactions

6) Motors - generating force for movement (flagella, actin filaments, etc)

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6
Q

How is a peptide bond formed?

A

Formed by a DEHYDRATION reaction linking one amino acid C-terminus to another amino acid N-terminus.

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7
Q

(T/F) In a linear polymer (polypeptide), there is a free amino end (N-terminus) and a free carboxyl end (C-terminus).

A

True!

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8
Q

Fill in the blank:

Protein function is derived from the ____ structure, which is determined by the aa sequence and ________ reactions.

A

3d; intramolecular

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9
Q

Define secondary structures.

A

Stable spatial arrangements of polypeptide chain segments held together by H bonds between backbone amine and carbonyl groups.

Alpha helix and beta sheets.

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10
Q

Which one of the statements regarding alpha helix is false?

1) They occur when the polypeptide backbone (ribbon) folds into a spiral/helix

2) Helix is stabilized by hydrogen bonds between backbone oxygen and hydrogen atoms (more bonds, more stable)

3) R groups project outward from the surface of the helix and determine the chemical nature of helix faces

4) Prolines are a major component of the alpha helix

A

4! Prolines cannot participate in H bonding and are usually excluded from alpha helix because they form kinks. Kinks constraints alpha helix from spiral.

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11
Q

What is a beta sheet? How is it stabilized?

A

LATERALLY packed beta strands, each of which is a nearly fully extended polypeptide segment.

Stabilized by H bonds between backbone oxygen and hydrogen atoms in amino acids on DIFFERENT STRANDS.

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12
Q

What is the difference between Antiparallel and Parallel beta sheets?

A

In parallel beta-sheets the strands all run in one direction (N-to-C), whereas in antiparallel sheets they all run in opposite directions.

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13
Q

What produces a pleated polypeptide backbone contour?

A

Alpha carbon bond angles

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14
Q

(T/F) In β sheets, alternate R groups project above and below the plane of the sheet.

A

True!

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15
Q

Fill in the blanks regarding a β turn.

A β turn is composed of _____ residues.

It ______ the direction of a polypeptide chain ( ____ U-turn)

Cα carbons of the first and the fourth residues are usually less than ____ nm apart and linked by a ______ bond.

A

four

reverses; 180°

0.7; hydrogen

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16
Q

What does the β turn facilitate?

A

β turns facilitate the folding of long polypeptides into compact structures.

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17
Q

Which amino acids are commonly found in β turns?

A

Glycine (smallest R group) and Proline (built in bend)

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18
Q

What are structural motifs? What can they be encoded by?

A

Structural motifs are regular combinations of secondary structures usually with a specific type of function.

They can be encoded by highly conserved sequence motif.

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19
Q

What are the three types of structural motifs?

A
  1. Coiled-coil motif
  2. EF hand/helix-loop-helix motif
  3. Zinc-finger motif
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20
Q

Answer the following questions regarding coiled-coil motif:

1) Briefly describe the structure.

2) At which positions do the alpha helix-heptad repeat sequence have a hydrophobic residue?

3) How is the seam stabilized?

A
  1. Two alpha helices that wound around each other. The hydrophilic molecules are outside, hydrophobic molecules are inside.
  2. At positions 1 and 4, there is a hydrophobic residue.
  3. Seam is stabilized by interactions between heptad 1 and 4 hydrophobic side chains!
21
Q

Where is zinc-finger motif present?

A

Zinc-finger motifs are present in many DNA-BINDING PROTEINS that help regulate TRANSCRIPTION.

22
Q

Fill in the blanks regarding zinc-finger motif:

It is composed of ____ amino acids with two INVARIANT _______ residues at position 3 and 6 and two INVARIANT _______ residues at position 20 and 24.

A

25; cysteine; histidine

*invariant means highly conserved; if you lose one of them, the motif can’t be formed.

*all organisms have these cys and his exactly in the same position.

23
Q

Cysteine and histidine interact to bind to Zinc(2+) between:

A

a pair of beta strands and a single alpha helix

24
Q

How is the tertiary structure stabilized?

A

1) Hydrophobic interactions between non-polar side chains.

2) Hydrogen bonds involving polar side chains and backbone amino and carboxyl groups.

25
Q

What happens to the hydrophobic residues in the tertiary structure?

A

They cluster together like drops of oil in the folded protein core, driven away from the aqueous surroundings by the HYDROPHOBIC EFFECT.

26
Q

What happens to the hydrophilic residues in the tertiary structure?

A

They (charged + uncharged polar side chains) form stabilizing interactions with surrounding water and ion on the protein surface.

27
Q

Fill in the blanks:

In the hemagglutinin (HA) tertiary structure, the distal domain (HA2) is the _______ domain and the proximal domain (HA1) is the _______ domain.

A

Globular; fibrous

28
Q

What does the hemagglutinin (HA) quaternary structure compose of?

How is it stabilized?

A

Three HA1-HA2 subunits.

It is stabilized by LATERAL INTERACTIONS between the long helices, forming a triple-stranded COILED-COIL stalk.

29
Q

What and where do the distal globular domain of the hemagglutinin quaternary structure bind to?

*hemagglutinin is an influenza virus surface protein

A

Sialic acid on the surface of target cells.

30
Q

(T/F) Approximately 20 percent of eukaryotic proteins have multiple structural domains.

A

False! Approximately 75 percent of eukaryotic proteins have multiple structural domains.

31
Q

Match the following terms to their definition regarding epidermal growth factor (EGF) domains:

1) EGF precursor
2) Neu
3) Tissue plasminogen activator (TPA)

A) Composed of EGF and other domains and breaks down blood clots

B) Generated by proteolytic cleavage that generates multiple EGFs

C) EGF domain plus another domain and is important for neural development

A

EGF precursor: Generated by proteolytic cleavage that generates multiple EGFs

Neu: EGF domain plus another domain and is important for neural development

Tissue plasminogen activator (TPA): Composed of EGF and other domains and breaks down blood clots

32
Q

(T/F) A protein can compose of multiple domains, while some domains are for structural activity other domains are for metabolic activity.

A

True!

33
Q

What is an example of a supramolecular complex?

A

Transcription initiation complex!

It is a molecular machine: Core RNA polymerase + general transcription factors, a mediator complex containing about 20 subunits and other protein complexes assemble at a gene promoter.

34
Q

Fill in the blank:

Protein function depends on binding ______.

A

Ligands (other molecules)

35
Q

How do enzymes accelerate rates of cellular reactions?

A
  1. Lower activation energy
  2. Stabilize transition state intermediates
36
Q

(T/F) Metabolic pathway enzymes may be associated as domains of a monomeric protein, subunits of a multimeric protein, or components of a protein complex assembled on a common scaffold.

A

True!

37
Q

(T/F) In all enzymes, like Trypsin, the catalytic site and the substrate-binding pocket are structurally distinct.

A

False!

In some enzymes, the catalytic site and the substrate-binding pocket OVERLAP.

38
Q

What side chains does the catalytic site of the trypsin contain?

A

Contains the side chains of the CATALYTIC TRIAD; Ser-195, Asp-102, and His-57, that BREAKS peptide bonds.

*some enzymes break peptide bonds, while others make.

39
Q

What are the functions of serine proteases?

A

1) Digest meals (tyrpsin, chymotyrpsin + elastase)

2) Control blood clotting (thrombin)

3) Help silk moths chew their way out of their cocoons (cocoonase)

40
Q

Fill in the blank:

Enzyme’s substrate binding site and catalytic site cooperate in _________ reaction to convert substrate to product.

A

Multistep

41
Q

What is the enzyme-substrate complex in equilibrium with?

A

EQUILIBRIUM with the unbound enzyme and substrate.

42
Q

The enzyme-substrate complex is the __________ step in the conversion of substrate to product.

A

INTERMEDIATE

43
Q

What does protein degradation do?

A
  1. Regulates the life spans of intracellular proteins (short as a few mins for mitotic cyclins to as long as the age of an organisms for proteins in the lens of the eye).
  2. Removes damaged proteins.
44
Q

Match the following steps of POLYUBIQUITINYLATION targeting proteins for PROTEASOMAL DEGRADATION:

1) Step 1
2) Step 2
3) Step 3
4) Step 4

A) E1 transfers the Ub molecule to a cysteine residue in E2.

B) E3 adds Ub molecules to the previously added Ub on the target protein

C) Enzyme E1 is activated by attachment of a ubiquitin (Ub) molecule

D) Ubiquitin ligase (E3) transfers the E2-bound Ub molecule to the side-chain - Nh2 of a lysine residue in a target protein, forming an isopeptide bond

A

Step 1: Enzyme E1 is activated by attachment of a ubiquitin (Ub) molecule

Step 2: E1 transfers the Ub molecule to a cysteine residue in E2.

Step 3: Ubiquitin ligase (E3) transfers the E2-bound Ub molecule to the side-chain - Nh2 of a lysine residue in a target protein, forming an isopeptide bond

Step 4: E3 adds Ub molecules to the previously added Ub on the target protein

45
Q

Match the final steps of ubiquitin and proteasome mediate proteolysis:

1) Recognition
2) Release
3) Unfolding
4) Transfer
5) Cleavage
6) Discharge

A) Deubiquitinase enzyme removes the Ub groups

B) A pore in the hexamer transfers the unfolded protein into the core proteolysis chamber.

C) Proteasome 19s cap Ub receptors bind the polyubiquitinylated target.

D) Cleaved peptides (2-24 residues long) are discharged and degraded by soluble proteases.

E) ATP hydrolysis enables the six-protein (hexameric) ATPase subunits to unfold the substrate.

F) Peptide bonds are cleaved.

A

1) Recognition: Proteasome 19s cap Ub receptors bind the polyubiquitinylated target.

2) Release: deubiquitinase enzyme removes the Ub groups

3) Unfolding: ATP hydrolysis enables the six-protein (hexameric) ATPase subunits to unfold the substrate.

4) Transfer: A pore in the hexamer transfers the unfolded protein into the core proteolysis chamber.

5) Cleavage: Peptide bonds are cleaved.

6) Discharge: Cleaved peptides (2-24 residues long) are discharged and degraded by soluble proteases.

46
Q

What are kinases and phosphotases?

A

Kinases phosphorylate proteins. Phosphotase de-phosphorylate proteins.

Both actions can activate some proteins and inactivate other types of proteins.

47
Q

(T/F) Most kinases can phosphorylate multiple different target proteins, and human genome encodes around 500 kinases (kinome).

A

True!

48
Q

(T/F) Kinome can only phosphorylate certain proteins.

A

False! They can phosphorylate members of all protein classes.