Lecture #6 - Haemoglobin variants

Question 1

What is haemoglobin? Like how many globing-folded proteins and how many helices in each?

Answer 1

4 globin-folded proteins consisting of 8 helical things

Question 2

HbF = fetal haemoglobin

1. Does it have lower affinity for oxygen than HbA?
2. What are the four subunits?
3. What effect does this change have on the interaction with BPG?
4. What happens to the Hb curve?

Answer 2

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Question 3

Looking at the curves of different normal global subunits during development

1. Alpha subunit - describe from start to birth
2. Gamma - describe from start to birth
3. Beta - describe from start to birth
4. When does the gamma and beta cross?
5. What are the axis for the graph?
6. What happens if still have alpha and gamma as adult?
7. Can get this transition because……

Answer 3

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Question 4

Temporal expression of globins from globin gene cluster

1. Globin genes encoded by either ___ or ____-globin gene clusters vary in their ____ ________ properties due to variations in the ____ ______ sequence
2. Each globin has evolved for ____ _____ during temporal human development e.g. what?
3. There are also non-expressed a and B-‘______’
   - what are they?

Answer 4

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Question 5

Abnormal variants of Hb that lead to anaemia or other pathological symptoms:

There are three of them - name them and their effect

Answer 5

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Question 6

HbS

1. Which subunit affected?
2. Which position is the mutant aa’ from the N-terminus?
3. Where is the mutant in the ____ helix?
4. Is it a surface location mutation?
5. What are the consequences?
6. How does it crystallise?
7. Is it Fe2+ or Fe3+

Answer 6

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Question 7

What is HbM? (med-haemoglobin)

Answer 7

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Question 8

Hb Boston:

1. What changes and what position (from N-terminus)?
2. What are the consequences? (3)

Answer 8

Consequences:

1. Heme moves a little so connection to F8 lost
2. HbM remains in ‘T state’ - all subunits have low affinity for oxygen
3. Fe2+ becomes Fe3+

Question 9

Hb Milwaukee

1. What changes and what position (from N-terminus)?
2. One consequence

Answer 9

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Question 10

When looking at the mutation map, are there more mutations to do with B or a subunits?

Answer 10

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Question 11

Hb Christchurch:

1. What subunit?
2. What aa’ from N-terminus?
3. What helix and what position?
4. Adjacent to what?
5. What is the wild type aa’ and what is the mutant aa’?
6. Consequences?

Answer 11

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Question 12

HbC:

1. What does this have to do with malaria?
2. What subunit?
3. What aa’ from N-terminus?
4. What helix and what position?
5. Surface or interior location?
6. What is the wild type aa’ and what’s the mutant?
7. What effect?

Answer 12

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