Session 4.3a - Lecture 1 - Protein Structure Flashcards
Slides 1-11
1
Q
ILO
A
- What do proteins do
- Structural aspects
- Think about how some of these things fit together and work
- E.g. enzymes
2
Q
Do NOT need to know all the molecular detail of the DNA repair pathways
A
Steve Foster lectures
3
Q
What was the take home message from SF lectures?
A
There are many different types of DNA repair mechanisms
4
Q
Why do we need many different types of DNA repair mechanisms?
A
Because DNA repair is very important; if things go wrong with DNA we need to put them right
5
Q
What can occur if DNA is damaged and not repaired?
A
If there are changes, that will affect DNA and therefore the function of the cell, so it is critically important to have DNA repair mechanisms
6
Q
Why do we need to know about DNA repair mechanisms?
A
We need to UNDERSTAND the importance of their role, as if DNA is not fixed then the function of the cell is changed
7
Q
What is non-homologous end joining (NHEJ)?
A
NHEJ is joining DNA when there’s a double stranded break.
Need to know BASICS but NOT all the proteins involved
8
Q
Why can NHEJ go wrong?
A
Although NHEJ is a neat process that repairs dsbreaks quite nicely, it is NOT very selective. This means that the process can be prone to errors.
9
Q
What can occur if NHEJ goes wrong?
A
Translocation events can occur.
10
Q
What are the levels to proteins?
A
Primary
Secondary
Tertiary and
Quaternary structure
11
Q
What are proteins made up from?
A
Amino acids
12
Q
How do proteins differ?
A
Although they are all made up from amino acids joined together, these tend to FOLD UP in different ways
13
Q
What is the primary structure of a protein?
A
Just the amino acids joined together
14
Q
What is the secondary structure of a protein?
A
The localised folding of the amino acid sequence
15
Q
What is the tertiary structure of a protein?
A
When the protein is folded up as a whole
16
Q
What is the quaternary structure of a protein?
A
When more than one subunit comes together to form a protein
17
Q
Fig. 2
Label the image
A
Left - proteins crystals used to get 3D structure of proteins
Primary structure
Secondary structure
Tertiary structure
Quaternary structure
18
Q
What is the relationship between protein structure and function?
A
Proteins fold up in different ways (due to their amino acid sequence) which relates to their function
19
Q
Why do we need to know about proteins, why are they important?
A
Proteins play crucial roles in virtually all biochemical processes - they do virtually everything in your cell that is of any consequence.
20
Q
What is the difference between DNA and protein?
A
DNA carries all the information but it’s the proteins that do things.
21
Q
What are the functions of proteins that are important in medicine?
A
- Catalysts
- Transporters
- Structural support
- Machines
- Immune protection
- Ion channels
- Receptors
- Ligands in cell signalling
22
Q
What is an example of proteins as catalysts?
A
Enzymes
23
Q
What are enzymes an example of?
A
Catalysts
24
Q
What is virtually every enzyme?
A
A protein (there might be other things associated with it but virtually all enzymes are proteins).
25
Give 2 examples of things proteins can transport
Oxygen and iron
26
Other than oxygen and iron around the body, where else can proteins transport things?
Things across cell membranes
27
What is the support in the body?
All support in body is really protein-based
28
What is an example of structural support in the body from proteins?
Collagens in skin and bone
29
What are the proteins found in bone, skin etc. that function as structural support?
- Collagen
| - Other scaffolding proteins
30
How do proteins act as molecular machines?
In muscular contraction and motion
31
What are the protein elements involved in muscles?
Actin and myosin
32
Where are actin and myosin found in muscles?
In sarcomeres
33
What is a sarcomere
The basic unit of striated muscle tissue.
34
How do proteins function for immune protection?
Immunoglobulins
35
What type of immunity is due to proteins?
Virtually all adaptive immunity down to role of proteins
36
What is the role of immunoglobulins?
Recognise any antigen effectively that comes into your body
37
What is the significance of proteins being immunoglobulins?
They need to recognise any antigen that comes into your body, which means there must be a huge repertoire of Igs! This can be produced by proteins because there are numerous different ways a protein can fold.
38
How are proteins important for cell communication?
They can form ion channels, receptors and ligands in cell signalling
39
What is the common function of ion channels, receptors and ligands?
Cell communication
40
What is the function of an ion channel?
For example, to set off electrical impulses in neuronal cells
41
What are receptors used for?
For hormones, neurotransmitters etc.
42
Give an example of a function of a receptor
Takes signals from outside the cell and passes to inside the cell - important for how you get hormonal regulation, for example.
43
Give an example of proteins as ligands in cell signalling
Growth factors
44
How are proteins and ligands interconnected?
Many proteins themselves will act as ligands - e.g. growth factors are protein-based.
45
What are the key features of proteins?
- Proteins are polypeptides
- The amino acid sequence of a protein is encoded by a gene
- The polypeptide chain folds into a complex and highly specific three-dimensional structure, determined by the sequence of amino acids
- The folding of proteins depends on the chemical and
physical properties of the amino acids
- The amino acid sequence of a protein is encoded by a gene
46
What are proteins?
Polypeptides - they are macromolecules made up of amino acids
47
What are polypeptides?
Chains of amino acids, aka proteins.
48
What is a macromolecule?
A big molecule
49
What is the simple unit of a protein?
An amino acid
50
What is the relation between amino acid and protein?
The amino acid is the simple repeating unit in a protein
51
What forms a protein?
Amino acids joined covalently to give the sequence of the protein (like beads on a strong)
52
How are amino acids joined together in proteins?
By strong covalent bonds known as peptide bonds.
53
What type of bond is a peptide bond?
Covalent (strong)
54
Fig. 4 (left)
Label this image
- Monomers
| - A linear polymer
55
What is another word for macromolecule?
Polymer
56
If a protein is a polymer, what is the monomer?
Amino acid
57
If an amino acid is a monomer, what is the polymer?
Protein
58
If a protein is a polymer, what is an amino acid?
Monomer
59
If an amino acid is a monomer, what is a protein?
Polymer
60
Fig. 4 (right)
What does this picture represent?
A protein sequence of amino acid, represented via a letter code (like genome sequences).
61
How are amino acids represented in a code by molecular biologists?
There is a 20-letter code (don't need to learn)
62
How is the amino acid sequence of a protein encoded for?
By a gene
63
What does a gene do in relation to proteins?
Encodes an amino acid sequence of a protein
64
What determines the amino acid sequence of a protein?
The nucleotide sequence of a gene
65
What does the nucleotide sequence of a gene determine?
The amino acid sequence of a protein
66
The amino acid sequence of a protein is encoded by a gene. What does this link?
This is critically important because it links your GENOME (nucleotide sequence) to your PROTEOME (protein sequence).
67
Define genome and proteome?
GENOME = nucleotide sequence
PROTEOME = protein sequence
68
Why is it important clinically to understand that DNA (genome) is linked to the protein (proteome)?
If you get a mutation in a GENE, you can affect the PROTEIN.
69
What is wrong with the beads on a string model of proteins?
Proteins don't really adopt that conformation - in some cases they do - but in most cases they fold up into a fine 3D structure
70
What determines the 3D structure of proteins?
The specific amino acid sequence that make up that particular protein
71
What does the amino acid sequence dictate?
The 3D structure of proteins
72
What is it about amino acids that affects the individuality of proteins?
The chemical and physical properties of those particular amino acid "residues" that make up a protein actually contribute to the 3D sequence of the protein.
73
What is the relation between the chemical and physical properties of an amino acid that make up a protein?
The properties of those particular amino acid "residues" (as we call them) that make up a protein actually contribute to the 3D sequence of the protein.
74
What is important about 3D structure?
3D structure often determines what a protein does.
75
Describe how amino acids are related to protein function?
The make up of a protein (its specific amino acid sequence) controls overall 3D shape and 3D shape defines its role.
76
What encodes the amino acid sequence of a protein?
A gene
77
What does a gene encode in proteins?
The amino acid sequence
78
How are nucleotides connected to genes?
The nucleotide sequence of a gene determines the amino acid sequence of a protein
79
How is expression of a protein dictated?
Unidirectionally (from DNA to protein)
80
How do we get from DNA to proteins?
- Gene contains our nucleotide sequence that encodes for a protein
- This gets converted to RNA by the process of TRANSCRIPTION
- We make the final protein by TRANSLATING that mRNA sequence
81
Fig. 6
Draw/fill in this simple diagram to explain DNA to protein formation.
```
DNA Replication
--Transcription-->
RNA
--Translation-->
Proteins
```
82
What are the basic building blocks of proteins?
Amino acids are the building blocks of proteins
83
What do amino acids consist of?
A central carbon atom (the a-carbon) covalently bonded to:
- an amino group (-NH2)
- a carboxyl group (-COOH)
- a hydrogen atom (-H)
- a distinctive R group (side chain)
84
What is the central carbon of an amino acid called?
The a-carbon
85
What is the a-carbon of an amino acid?
The central carbon
86
How is the central carbon of an amino acid connected to the other groups?
By covalent bonds
87
What is the amino group?
-NH2
88
What is -NH2 called?
An amino group
89
What is the carboxyl group?
-COOH (remember, it is not actually a carbon bonded to an oxygen to a hydrogen: got a slightly different structure)
90
What is -COOH called?
Carboxyl group
91
What does H stand for?
Hydrogen atom
92
What is the R group?
A distinctive side chain
93
What is the side chain of an amino acid?
The distinctive R group
94
Draw the general structure of an amino acid.
Ca
- NH2
- COOH
- R
- H
95
Fig. 7
Caption this image
General structure of an amino acid
96
What is the significance of the alpha carbon in terms of structure?
Because there are 4 DIFFERENT groups around this carbon then these often have stereoisomers.
97
Why can amino acids be stereoisomers?
Because there are 4 different groups around the central a-carbon
98
A central carbon with 4 different groups attached to it is called what?
A stereoisomer
99
What significance is there in amino acids being stereoisomers?
There are isomeric forms of amino acids in most cases.
100
Isoleucine is normally found in a powder.
What would the structure be of isoleucine taken from a powder in a bottle?
It would have the generalised structure - i.e. NOT IONISED
101
Isoleucine is normally found in a powder.
What would happen to the structure of an amino acid if we put it into water, i.e. make a solution out of it?
It would become ionised (no longer the general structure of an amino acid)
102
What is the significance of the presence of both an amino and carboxyl group on an amino acid?
This gives us ionisation states of amino acids
103
Fig. 8
Caption the images
Unionised form of amino acid (left)
Ionised form of amino acid (right)
104
Draw the unionised and ionised form of amino acids?
Ca-R-H on both
Unionised - NH2, COOH
Ionised - NH3+, COO-
105
What can ionise on an amino acid?
Both the carboxyl group (-COOH) and the amino group (-NH2) can ionise, and potentially the side chain
106
What do we mean by ionise (in relation to amino acids)?
Simply, they will form ions
107
What form does an amino acid take in solution?
The ionised form
108
*Example ESA1 question*
Draw an amino acid in solution.
Draw the IONISED form
- make sure you draw the ionised form!
NH3+, COO-
109
What happens to the amino and carboxyl group of amino acids in solution?
Protonated amino group NH3+
Deprotonated carboxyl group COO-
110
Why do we get the ionised structure in solution?
The carboxyl group acts as an acid and the amino group acts as a base.
111
Which group of the amino acid acts like an acid?
The carboxyl side chain (carboxylic acid)
112
What are acids?
Proton donors
113
What do we call groups that can donate a proton?
Acids
114
Acidic side chains donate their proton to do what?
Become ionised
115
How do acidic side chains become ionised?
By donating a proton
116
What is the dissociation equation for carboxylic acid?
COOH COO- + H+
117
What form will carboxylic take at physiologic pH?
COO-
It will always, or mostly be, in COO- form.
118
What does the amino group of an amino acid act as?
A base
119
What acts as a base in the amino acid?
The amino group
120
How do bases function chemically?
They attract protons
121
What do we call groups that attract protons?
Bases
122
What can become protonated on an amino acid?
The NH2 group/the base
123
What is the consequence of the NH2 group attracting a proton?
It becomes positively charged
124
What is the dissociation equation for amino groups?
NH2 + H+ NH3+
125
What is the significance of the equilibrium in this equation?
NH2 + H+ NH3+
NH3+ can act as an acid and become NH2
126
Why is it important to note that acid and base equations are equilibrium equations?
One side of the equation acts as an acid and the other side acts as a base.
127
What do we call a compound that is doubly charged with 0 net charge?
A zwitterion
128
What is a zwitterion?
A molecule or ion having separate positively and negatively charged groups with an overall net charge of 0
129
Why are amino acids called zwitterions?
In solution, they have separate positively (NH3+) and negatively charged groups (COO-) [The side chain has not been included].
130
How do we classify amino acids?
Classified according to the chemical properties of the R (side chains) groups.
131
Why do we classify AA according to their side chain/R group?
The amino and carboxyl group of proteins (with the exception of the ones at the end) are covalently bonded to adjacent amino acids creating a peptide bond, thus being unavailable for reaction.
It is therefore the amino acid side chain that is available for chemical reaction and causes the chemical properties of a protein.
132
Fig. 9
What is this structure?
A very small protein, or peptide
133
What do we call a very small protein?
Peptide
134
What is a peptide?
A very small protein
135
What do we find at the N-terminal end of a protein?
A free amino group
136
Where is a free amino group found on a protein?
At the N- or amino-terminal end
137
Fig. 9
Label the first two amino acids.
Serine (CH2OH)
| Glycine (H)
138
Fig. 9
Identify a peptide bond
Yellow
139
Fig. 9
What do the yellow and red represent?
Red - side chains
| Yellow - peptide bonds
140
How are peptide bonds formed?
Between carboxyl group of one amino acid and amino group of another
141
What is found between the carboxyl group of one amino acid and an amino group of another?
Peptide bond
142
What does a peptide bond do and what does this mean chemically?
Bind two amino acids together, meaning they lose their amino and carboxyl groups
143
How often do peptide bonds occur in amino acids?
Between all amino acid residues in this peptide
144
Where is there a free carboxyl group in an protein?
At the C- or Carboxyl-terminus end
145
What do you find at the C- or Carboxyl-terminus end of a protein?
A carboxyl group
146
What are the ends of a protein called and what do you find there?
N- or amino-terminal end
NH3+/NH2
C- or carboxyl-terminal end
COO-/COOH
147
What causes the chemical properties of a protein?
The side chains of the individual amino acids each makes up.
148
Fig. 9
Label the diagram as fully as possible
Amino-terminal end (NH3+)
Carboxyl-terminal end (COO-)
Yellow = peptide bond
Red = side chains
Black C = central carbon
Amino acid = circle around central carbon atom and edges between C-N
Amino acid sequence = serine, glycine, tyrosine, alanine, leucine
149
Draw a peptide from N- to C- terminus containing serine, glycine, tyrosine, alanine and leucine.
```
Amino-terminal end NH3+-
C-H-CH2OH-C=O-N-H-
C-H-H-C=O-N-H-
C-H-CH2-benzene-OH-C=O-N-H-
C-H-CH3-C=O-N-H-
C-H-CH2-CH-CH3-CH3-C=O-N-H-
-COO- Carboxyl-terminal end
```
150
How many aNH3+ are there?
Only 1
151
How many aCOO- are there?
Only 1
152
Where is the aNH3+?
At the N-terminal end
153
Where is the aCOO-?
At the C-terminal end
154
What is at the N-terminal end?
aNH3+
155
What is at the C-terminal end?
aCOO-
156
What is determined by the R groups?
Acid-base behaviour
157
How is acid-base behaviour determined in proteins?
By the R groups
158
What is an amino acid residue?
An amino acid residue is what remains of an amino acid after it has been joined by a peptide bond to form a protein
159
When do we think about amino acids, as opposed to amino acid residues?
AA - When they're in solution
AAR - in a protein
160
What do we find in the constituents of a protein?
Amino acid RESIDUES
161
Where are amino acid RESIDUES found?
In the constituents of a protein
162
Fig. 10
Label these images and name the amino acid
Amino acid
Amino acid residue
Alanine
163
Draw alanine as an amino acid and an amino acid residue
Amino acid:
C-[COO-]-H-[NH3+]-CH3
Amino acid residue:
C-[C=O]--H-[N-H]--CH3
164
What are the functional properties of an amino acid residue?
Lost its amino and carboxyl group so only have a side chain
165
How should we refer to amino acids:-
Amino acid or amino acid residue?
We should always term them amino acid residues when we're talking about how they are in proteins; the carboxyl and amino groups are joined together by a peptide bond
166
What do these represent in amino acids?
Hydrophobic, hydrophilic, polar, non-polar, acidic, basic, neutral, aliphatic, aromatic etc.?
Classified according to the chemical and physical properties of the R groups
167
How can amino acids be classified?
Chemical properties
- Hydrophobic
- Hydrophilic
- Polar
- Non-polar
- Acidic
- Basic
- Neutral
Physical properties
- Aliphatic
- Aromatic
168
How can amino acids be classified according to their chemical properties?
- Hydrophobic
- Hydrophilic
- Polar
- Non-polar
- Acidic
- Basic
- Neutral
169
How can amino acids be classified according to their physical properties?
- Aliphatic
| - Aromatic
170
What do hydrophobic and hydrophilic mean?
Hydrophobic = water-hating
Hydrophilic = water-loving
171
What are the words to define water-hating and water-loving?
Hydrophobic = water-hating
Hydrophilic = water-loving
172
If a molecule has a partial charge it is considered _____
Polar
173
If a molecule does not have a partial charge it is considered _____
Non-polar
174
A polar molecule has a _______ ______
PARTIAL charge
175
A non-polar molecule _____ ___ have a _______ ______
Does not have a partial charge
176
Polar is effectively the same as _________ in terms of classification
Hydrophilic
177
Non-polar is effectively the same as _________ in terms of classification
Hydrophobic
178
Hydrophilic is effectively the same as _________ in terms of classification
Polar
179
Hydrophobic is effectively the same as _________ in terms of classification
Non-polar
180
We can define whether an amino acid is polar or not into further categories
Acidic
Basic
Neutral
181
What is a neutral amino acid?
No overall charge
182
What is an amino acid with no overall charge?
Neutral
183
Neutral amino acids can still be polar - true or false?
Why?
True
They can have groups that can become charged but at physiological pH they are not, because they are weak acids/bases
184
What charges do acidic or basic amino acids have on them?
Acidic = -ve charge
Basic = +ve charge
185
Negative and positively charged amino acids can be classified into ___?
Acidic = -ve charge
Basic = +ve charge
186
Why do we want to know how to classify amino acids?
Classifying by their chemical properties (and physical properties) enables us to see how the final protein works.
187
Why do we classify amino acids based on shape?
There are many different shapes/sizes/structures of amino acids (these ultimately can affect their chemical properties)
188
Define aromatic
Has a ring-like structure
189
Define aliphatic
Long chain of carbons and hydrogens
190
What chemical term can be used to describe a molecule that has a ring-like structure?
Aromatic
191
What chemical term can be used to describe a molecule that is composed of a long chain of carbons and hydrogens
Aliphatic
