Protein Structure and Diversity - Proteins

Question 1

What is the wwPDB?

Answer 1

World-Wide Protein Data Bank

Question 2

The wwPDB is mainly made up of three types of data, what are they and how much do they each contribute (%)?

Answer 2

• X-ray crystallography 89%
• NMR 8%
• Electron Cryo-microscopy 4%
  (101% lol idk that’s what it says on my handout)

Question 3

What is the primary structure of a protein?

Answer 3

It’s amino acid sequence

Question 4

What is the bond formed between amino acids and what is the dihedral bond angle?

Answer 4

• Peptide or amide bond
• 180 ± 10 it is mostly planar (staggered conformation)

Question 5

What is usually the first amino acid and why?

Answer 5

Methionine as the start codon AUG codes for it

Question 6

What group does Glycine, Alanine, Valine, Leucin, Isolucine and Proline belong to and how do they contribute to tertiary/quaternary structures?

Answer 6

Hydrophobic residues - they stick together and stay away from water

Question 7

What group does Tyrosine belong to and how do they contribute to tertiary/quaternary structures?

Answer 7

Aromatic and polar - can form pi stacking with other aromatic rings

Question 8

What group does Phenylalanine and Tryptophan belong to and how do they contribute to tertiary/quaternary structures?

Answer 8

Aromatic and not polar - can form pi stacking with other aromatic rings

Question 9

What group does Methionine and Cysteine belong to and how do they contribute to tertiary/quaternary structures?

Answer 9

Sulfurous - they form disulfide bond

Question 10

What group does Threonine, Serine, Glutamine and Asparagine belong to and how do they contribute to tertiary/quaternary structures?

Answer 10

Polar and uncharged - they are happy to be exposed to water

Question 11

What group does Histidine, Lysine and Arginine belong to and how do they contribute to tertiary/quaternary structures?

Answer 11

Basic - they form salt bridges with positive side chains

Question 12

What group does Glutamic acid and Aspartic acid belong to and how do they contribute to tertiary/quaternary structures?

Answer 12

Acidic - they form salt bridges with negative side chains

Question 13

What is secondary structure?

Answer 13

The recurring arrangement of the amino acid sequence - split into alpha helixes and beta strands

Question 14

What are the three types of secondary structures?

Answer 14

Alpha helixes, parallel beta strands and antiparallel beta strands

Question 15

How are alpha helixes and beta strands stabilized?

Answer 15

By H-bonding between side chains

Question 16

Are parallel or anti-parallel beta sheets more stable?

Answer 16

Anti-parallel beta sheets are more stable due to an increased number of hydrogen bonds

Question 17

What are tertiary structures?

Answer 17

How alpha and beta secondary structures are arranged in space

Question 18

What are the 5 main causes of tertiary structure?

Answer 18

1) Disulfide bonds
2) Salt bridges (pH dependent)
3) Hydrophobic forces (stick together)
4) van der Waals repulsions
5) Metal ion coordination

Question 19

What does a thioredoxin fold tertiary structure look like?

Answer 19

Beta sheets at the core and alpha helixs at the edge

Question 20

What does a greek key fold tertiary structure look like?

Answer 20

Antiparallel beta sheets - form a Y structure found in antibodies

Question 21

What does a TIM barrel fold tertiary structure look like?

Answer 21

Alternating alpha and beta structures with the beta strands parallel to each other

Question 22

What does an EF hand fold tertiary structure look like?

Answer 22

Helix-turn-helix with an ion coordination in the turn

Question 23

What does a Rossmann fold tertiary structure look like?

Answer 23

Alternating beta and alpha structures with the beta strands parallel to each other

Question 24

What does a Jelly Roll fold tertiary structure look like?

Answer 24

Antiparallel beta strands

Question 25

What is quaternary structure?

Answer 25

The arrangement of various tertiary folds in space

Question 26

What are the forces involved in quaternary structure?

Answer 26

- Optimisation of tertiary structure forces - Often driven by symmetry

Question 27

What is the difference between homo-oligomers and hetero-oligomers?

Answer 27

Homo-oligomers are made of many of the same protein whereas hetero-oligomers are made of multiple different proteins

Question 28

What is a silent mutation?

Answer 28

When a mutation in a codon still leads to the same amino acid being synthesized

Question 29

What a co-translational modifications?

Answer 29

When a protein is modified as it is being created

Question 30

What is homology between two proteins?

Answer 30

They share a common ancestor - and probably have similar function depending on how much their amino acid sequences have diverged

Question 31

What are paralouges?

Answer 31

Two genes with a common ancestor and the same species

Question 32

What are orthologues?

Answer 32

Two genes with a common ancestor but from different species

Question 33

What are analogues?

Answer 33

Two genes with similar function but from unrelated genes

Question 34

How can we infer homology from a protein?

Answer 34

By aligning their amino acid sequences to calculate the degree of conservation

Question 35

What is a point mutation, insertion and deletion in terms of types of mutations?

Answer 35

- Point mutation: Change of one residue to another one - Insertion: Added to the gene - Deletion: Removal from the gene

Question 36

What are gene duplications, exon shuffling and mRNA splicing?

Answer 36

- Gene duplications: the genes can each undergo separate mutations so although they will be homologous but with slightly different functions - Exon shuffling: exons from multiple genes combine resulting in very different structures mRNA splicing: stress response in plants leading to different lengths and activities

Question 37

What is homology modeling?

Answer 37

Trying to locate domains of a problem protein that match with chunks of well known proteins

Question 38

What is PAE (Predicted Aligned Error)?

Answer 38

Is a prediction in the error of alignment of domains in a protein when calculated by a deep-learning program