Secondary Structure Flashcards
Protein Secondary Structure
The assignment of helices and sheets – the local spatial conformation of a polypeptide’s backbone.
What is the α-helix?
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.
What is the α-helix also known as?
3.613 helix
* 3.6 amino acids in each turn of the helix
* 13-member ring is formed by hydrogen bonding
What is the significance of the hydrogen bonding in the α-helix?
The sum of the hydrogen bonds in a helix makes it quite stable.
Each hydrogen bond is relatively weak in isolation
What were the two key developments in the modelling of the α-helix?
- The correct bond geometry, thanks to crystal structure determinations of amino acids and peptides
- Pauling’s prediction of planar peptide bonds; and his relinquishing of the assumption of an integral number of residues per turn of the helix.
What is the hydrogen bonding pattern in the α-helix?
The i + 4 -> i hydrogen bonding pattern is observed in the α-helix
What was the pivotal moment in the development of the α-helix model?
- 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
Who did Pauling work with to confirm his model of the α-helix before publication?
Corey and Branson
What was Linus Pauling awarded his first Nobel Prize for?
in 1954
“for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances”.
What are β-strands?
- usually 5-10 amino acids in length,
- residues forming an almost fully extended zig-zag conformation.
What is the β-sheet?
- A structure formed by two or more β-strands
What are the three types of β-sheets?
- Parellel
- Anti-parallel
- Mixed
Parallel β-sheets
When β stretches are running in the same direction
from N-term to C-term
Anti-parallel β-sheets
Successive strands of alternating directions
N-term to C-term followed by C-term to N-term
Mixed β-sheets
Containing both parallel and anti-parallel strands
What are loops & turns in proteins?
Regions of proteins that connect segments of α-helices or β-strands
Characteristics of loops & turns
- 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
What is a β-turn or β-bend?
- 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.
How is β-turn or β-bend stabilised?
In part by the formation of a hydrogen bond between C=O of the first residue and NH of the fourth residue
What amino acids are most commonly associated with the α-helix?
- Glutamic Acid
- Methionine
- Alanine
- Leucine
Which amino acid is commonly associated with minimizing steric hindrance and why?
Glycine due to its small side chain.
Which amino acid is commonly associated with introducing a kink or bend in the polypeptide backbone?
Proline due to its unusual structure
What are domains?
tightly folded subregions of a single polypeptide connected to each other by more flexible or extended regions
What are motifs?
Motifs are building blocks of domains
Composed of a few stretches of secondary structure arranged in a specific 3-D conformation.
What is the function of domains in proteins?
Often serve as independent units of function
such as:
* substrate binding
* catalyzing enzymatic reactions
What are the three types of domains?
- α domain
- β domain
- αβ domain.
α domain
- Domains core structure built exclusively from stretches of α-helix
- four-helical bundle structure single most common motif contributing to this
β domain
- Structure displays a core comprising of anti-parallel β sheets
- Two sheets packed together
- Form distorted barrel-like structure
αβ domain
- Consist of combinations of β-α-β motifs that form parallel β-sheets surrounded by stretches of α-helix.
- Most common domain types.
What are some examples of structural motifs?
- helical bundle
- β-hairpin
- Greek key motif,
- Jelly roll
- β-sandwich
- β-barrel.
What is the helical bundle?
- Structural motif
Several stretches of α-helix separated by short bends or loops. - Axis is sometimes twisted
Are α-helical elements in the helical bundle parallel or antiparallel to each other?
α-helical elements are usually (though not always) almost fully parallel or antiparallel to each other in the helical bundle.
What are some examples of different numbers of constituent helical stretches in the helical bundle?
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.
What is the β-hairpin?
A simple structural motif
Two stretches of β secondary structure connected by a loop.
What is the Greek key motif?
- 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.
What is the Jelly roll?
- two closely associated Greek key motifs
- forming a nearly fully closed structure.
What is the β-sandwich?
- Two β-sheets packed face to face against each other.
- Associated with nucleotide binding proteins
β-sandwich variation
αβα sandwich layer
β sheet between two α-helical sturctures
What is the β-barrel?
- 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.
β-barrel variation
α/β barrel
Composed of alternating α and β stretches
What are porins?
non-selective transmembrane channels in the outer membrane of Gram-negative bacteria.
What is the structure of porins?
Consist of trimeric structures integrated into the outer membrane
* Hydrophobic residues oriented toward the exterior
* Hydrophilic residues oriented toward the interior pore.
When was OmpF porin first crystallized?
1979 by R. M. Garavito
