Proteins and protein structure
Introduced| English | Meaning |
|---|---|
| primary structure/ˈpraɪməri ˈstrʌktʃə/ | The sequence of amino acids in a polypeptide chain. |
| secondary structure/ˈsekəndəri ˈstrʌktʃə/ | Local folding such as α-helices and β-sheets held by backbone hydrogen bonds. |
| tertiary structure/ˈtɜːʃjəri ˈstrʌktʃə/ | The overall 3-D shape of one polypeptide, held by side-chain interactions. |
| quaternary structure/kwəˈtɜːnəri ˈstrʌktʃə/ | The arrangement of several polypeptide subunits in one protein, as in haemoglobin. |
| haemoglobin/ˌhiːməˈɡləʊbɪn/ | The iron-containing protein in red blood cells that binds and transports oxygen. |
| sigmoid curve | sigmoid curve |
| cooperativity | Binding at one site changing the affinity of the other sites, as in haemoglobin. |
| Bohr effect/ˈbəʊə ɪˈfekt/ | Bohr effect |
| sickle cell disease | A primary-structure change with quaternary results. |
The cell's workforce
- Enzymes, transporters, antibodies, receptors: nearly everything a cell does, a protein does.
- Structure is not decoration. Each level builds on the last, and each level is a place a mutation can break.
Four levels of structure
- Primary structure 一级结构 is the amino-acid sequence, read N→C. Secondary structure 二级结构 is the α-helix and β-sheet, held by backbone hydrogen bonds.
- Tertiary structure 三级结构 is the full 3D fold around a water-avoiding core. Quaternary structure 四级结构 is how several chains assemble.
Put the levels of protein structure in order, from simplest to most complex.
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Each level is built on the one before, so a change at the sequence level can show up at every level above it.
The reference protein
- Haemoglobin 血红蛋白 (Hb) is four chains, $\alpha_{2}\beta_{2}$, with four haem groups: 64.5 kDa and up to 4 O₂ per molecule.
- Myoglobin, one chain with one haem, stores O₂ in muscle. Comparing the two shows what the quaternary level adds.
Haemoglobin has a quaternary structure but myoglobin does not. Why?
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Quaternary structure is the assembly of several chains. One chain (myoglobin) cannot have it; Hb's α₂β₂ tetramer does.
Binding helps binding
- Myoglobin's O₂ curve is a simple hyperbola. Haemoglobin's is a sigmoid curve S形曲线: each bound O₂ shifts the chains from the low-affinity T state to the high-affinity R state.
- This cooperativity 协同效应 (Hill coefficient about 2.8, maximum 4) loads Hb fully in the lungs (100 mmHg) and unloads about 25% in resting tissue (40 mmHg), over 60% in working muscle (20 mmHg).
Myoglobin binds O₂ cooperatively, giving a sigmoid curve.
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Myoglobin has one site, so its curve is a hyperbola. Cooperativity needs several sites that influence each other, as in Hb.
Worked example: how much O₂ blood carries
- 15 g of Hb per dL ÷ 64 500 g per mol = 233 µmol per dL. Four sites give 930 µmol O₂, which is 20.8 mL O₂ per dL at 22.4 mL per mmol.
- That is 1.39 mL per g in theory. The measured value is 1.34 mL per g, so 20.1 mL per dL: some Hb is in forms that cannot carry O₂.
A patient with anaemia has 9 g of Hb per dL. Using the measured 1.34 mL O₂ per g, how much O₂ can each dL of blood carry, in mL?
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9 × 1.34 = 12.1 mL O₂ per dL, against 20.1 at 15 g per dL: capacity falls in step with Hb, whatever the lungs do.
Shifting the curve
- H⁺ and CO₂ lower Hb's affinity (the Bohr effect 波尔效应), so active tissue gets more O₂. 2,3-BPG binds the T state and helps unloading, for example at altitude.
- Fetal Hb binds 2,3-BPG weakly, so its curve sits to the left and it pulls O₂ from the mother's blood.
Match each factor to its effect on haemoglobin.
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Each shifts the same curve; right shifts help unloading, a left shift helps loading.
Worked example: one charged bead
- (Fictional patient) In HbS one amino acid changes: glutamate to valine at position 6 of the β chain. A charged surface patch becomes water-avoiding.
- In the deoxy T state it docks into a neighbour, Hb molecules polymerise and the red cell sickles and blocks small vessels. Sickle cell disease 镰状细胞病 is a primary-structure change with quaternary results.
Why does the Glu6Val change in HbS cause sickling?
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One bead in the sequence changes how whole molecules stick together in the T state, and the stiff polymer bends the cell.
Three common slips
- "Denaturation breaks peptide bonds." It unfolds the protein; the sequence survives.
- "All mutations are equally bad." A similar amino acid on the surface may be silent; a change in the core or active site rarely is.
- Forgetting Hb's other ligands. H⁺, CO₂ and 2,3-BPG all shift the curve, and physiology lives on those shifts.
Heating a protein until it denatures breaks its peptide bonds.
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Denaturation unfolds secondary, tertiary and quaternary structure; the covalent sequence (primary structure) stays intact.
Recap
- Sequence → local shapes → 3D fold → assembly; each level can break.
- Hb is a cooperative tetramer: sigmoid binding, Hill coefficient about 2.8, about 20 mL O₂ per dL of blood.
- One changed amino acid (Glu6Val) can change how whole molecules assemble.