Secondary Structure

Question 1

Protein Secondary Structure

Answer 1

The assignment of helices and sheets – the local spatial conformation of a polypeptide’s backbone.

Question 2

What is the α-helix?

Answer 2

The α-helix is a coiled or spiral conformation in which every backbone carbonyl oxygen (C=O) group forms a hydrogen backbone amide (N-H) group of the amino acid four residues ahead of it in the helix.

Question 3

What is the α-helix also known as?

Answer 3

3.613 helix
* 3.6 amino acids in each turn of the helix
* 13-member ring is formed by hydrogen bonding

Question 4

What is the significance of the hydrogen bonding in the α-helix?

Answer 4

The sum of the hydrogen bonds in a helix makes it quite stable.
Each hydrogen bond is relatively weak in isolation

Question 5

What were the two key developments in the modelling of the α-helix?

Answer 5

1. The correct bond geometry, thanks to crystal structure determinations of amino acids and peptides
2. Pauling’s prediction of planar peptide bonds; and his relinquishing of the assumption of an integral number of residues per turn of the helix.

Question 6

What is the hydrogen bonding pattern in the α-helix?

Answer 6

The i + 4 -> i hydrogen bonding pattern is observed in the α-helix

Question 7

What was the pivotal moment in the development of the α-helix model?

Answer 7

• In 1948
• Pauling drew a polypeptide chain of roughly correct dimensions on paper and folded it into a helix being careful to maintain planar peptide bonds.
• After a few attemps he produced a model with physically plausible hydrogen bonds

Question 8

Who did Pauling work with to confirm his model of the α-helix before publication?

Answer 8

Corey and Branson

Question 9

What was Linus Pauling awarded his first Nobel Prize for?

Answer 9

in 1954
“for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances”.

Question 10

What are β-strands?

Answer 10

• usually 5-10 amino acids in length,
• residues forming an almost fully extended zig-zag conformation.

Question 11

What is the β-sheet?

Answer 11

• A structure formed by two or more β-strands

Question 12

What are the three types of β-sheets?

Answer 12

• Parellel
• Anti-parallel
• Mixed

Question 13

Parallel β-sheets

Answer 13

When β stretches are running in the same direction

from N-term to C-term

Question 14

Anti-parallel β-sheets

Answer 14

Successive strands of alternating directions

N-term to C-term followed by C-term to N-term

Question 15

Mixed β-sheets

Answer 15

Containing both parallel and anti-parallel strands

Question 16

What are loops & turns in proteins?

Answer 16

Regions of proteins that connect segments of α-helices or β-strands

Question 17

Characteristics of loops & turns

Answer 17

• Vary in length and shape
• Allow the polypeptide to fold into a compact tertiary structure.
• Present on the surface of polypeptides
• Rich in polar/charged aa
• Quite flexible
• Often form the active sites of enzymes

Question 18

What is a β-turn or β-bend?

Answer 18

• Characteristic feature of many polypeptides
• A loop structure that achieves a 180˚ alteration in backbone direction over the course of 4 amino acid residues
• Most often found between two stretches of antiparallel β-strands.

Question 19

How is β-turn or β-bend stabilised?

Answer 19

In part by the formation of a hydrogen bond between C=O of the first residue and NH of the fourth residue

Question 20

What amino acids are most commonly associated with the α-helix?

Answer 20

• Glutamic Acid
• Methionine
• Alanine
• Leucine

Question 21

Which amino acid is commonly associated with minimizing steric hindrance and why?

Answer 21

Glycine due to its small side chain.

Question 22

Which amino acid is commonly associated with introducing a kink or bend in the polypeptide backbone?

Answer 22

Proline due to its unusual structure

Question 23

What are domains?

Answer 23

tightly folded subregions of a single polypeptide connected to each other by more flexible or extended regions

Question 24

What are motifs?

Answer 24

Motifs are building blocks of domains
Composed of a few stretches of secondary structure arranged in a specific 3-D conformation.

Question 25

What is the function of domains in proteins?

Answer 25

Often serve as independent units of function
such as:
* substrate binding
* catalyzing enzymatic reactions

Question 26

What are the three types of domains?

Answer 26

• α domain
• β domain
• αβ domain.

Question 27

α domain

Answer 27

• Domains core structure built exclusively from stretches of α-helix
• four-helical bundle structure single most common motif contributing to this

Question 28

β domain

Answer 28

• Structure displays a core comprising of anti-parallel β sheets
• Two sheets packed together
• Form distorted barrel-like structure

Question 29

αβ domain

Answer 29

• Consist of combinations of β-α-β motifs that form parallel β-sheets surrounded by stretches of α-helix.
• Most common domain types.

Question 30

What are some examples of structural motifs?

Answer 30

• helical bundle
• β-hairpin
• Greek key motif,
• Jelly roll
• β-sandwich
• β-barrel.

Question 31

What is the helical bundle?

Answer 31

• Structural motif
  Several stretches of α-helix separated by short bends or loops.
• Axis is sometimes twisted

Question 32

Are α-helical elements in the helical bundle parallel or antiparallel to each other?

Answer 32

α-helical elements are usually (though not always) almost fully parallel or antiparallel to each other in the helical bundle.

Question 33

What are some examples of different numbers of constituent helical stretches in the helical bundle?

Answer 33

Different numbers of constituent helical stretches may occur in the helical bundle.
Eg. several cytokines have a 4 helical bundle while cytochrome C oxidase has a 22 helical bundle.

Question 34

What is the β-hairpin?

Answer 34

A simple structural motif
Two stretches of β secondary structure connected by a loop.

Question 35

What is the Greek key motif?

Answer 35

• 4 adjacent antiparallel strands and their linking loops
• 3 antiparallel strands connected by hairpins while 4th is adjacent to 1st and linked to 3rd by longer loop

forming easily during the protein folding process.

Question 36

What is the Jelly roll?

Answer 36

• two closely associated Greek key motifs
• forming a nearly fully closed structure.

Question 37

What is the β-sandwich?

Answer 37

• Two β-sheets packed face to face against each other.
• Associated with nucleotide binding proteins

Question 38

β-sandwich variation

Answer 38

αβα sandwich layer
β sheet between two α-helical sturctures

Question 39

What is the β-barrel?

Answer 39

• An assemblage of stretches of β-strands folded into a barrel-like structure.
• Can consist of 5 to 16 individual β-strands
• Beta-strands in beta-barrels are typically arranged in an antiparallel fashion.

Question 40

β-barrel variation

Answer 40

α/β barrel
Composed of alternating α and β stretches

Question 41

What are porins?

Answer 41

non-selective transmembrane channels in the outer membrane of Gram-negative bacteria.

Question 42

What is the structure of porins?

Answer 42

Consist of trimeric structures integrated into the outer membrane
* Hydrophobic residues oriented toward the exterior
* Hydrophilic residues oriented toward the interior pore.

Question 43

When was OmpF porin first crystallized?

Answer 43

1979 by R. M. Garavito