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L3 - Anatomy of Protein Structure

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Extensive notes on lectures for module 6BBB0333 Protein Structure & Design lecture 3 on anatomy of protein structure.

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February 19, 2025
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6BBB0333


L3 – Anatomy of Protein Structure



Super-secondary structure/motifs

Definition: Elements of secondary structure (helices, β-strands) can be combined to form “motifs” or
super-secondary structure
Simple combinations of a few secondary structure
- Some motifs confer biological function elements with a specific geometric arrangement
have been found to occur frequently in protein
structures. These units have been called either
Helix-turn-helix motif supersecondary structures or motifs. Some of
these motifs can be associated with a particular
- Two alpha helices joined by short turn function such as DNA binding; others have no
- Involved in DNA binding (biological function) specific biological function alone but are part of
- E.g. Bacteriophage Lambda Cro Protein larger structural and functional assemblies.




This is the simplest
motif with a
specific function




Helix-loop-helix

- Two alpha helices joined by loop region
- EF hand is a type of HLH
- Present in calmodulin (Calcium-binding motif)
- E.g. Calmodulin (calcium-binding motif)




What are structural motifs?: motifs that do not form stable domains on their own

,6BBB0333


Some motifs form part of a larger structure and might not necessarily form a stable structural unit
on their own; e.g. B-hairpin and Greek key motifs



B-hairpin motif

- Simplest type of structural motif (super-secondary structure) – even simpler than HLH motif
- No specific function associated with this motif
- 2 adjacent ANTI-parallel beta strands joined by short loop or turn (link region)
- Multiple join to form a B sheet
o A variety of connections between the two strands can exist (e.g. reverse turn)
- E.g. found in Streptococcal protein G
o Binds antibodies
o 2 hairpin motifs




their frequent occurrence compared with
Greek key motif other arrangements of four antiparallel b
strands is based on an initial formation of one
- Structural motif long antiparallel structure with loops in the
- 4 antiparallel beta strands middle of both b strands, as shown in Figure
- Contributes to part of a beta barrel structure 2.16. By structural changes in the loop regions
- Found in trypsin (serine protease) between b strands 1 and 2 and between b
o Only forms very small part of overall structure strands 3 and 4, the top part folds down so
o Motif contributes to formation of beta barrel that b strand 2 associates with b strand 1. Beta
strands 1 and 2 then form hydrogen bonds,
and the Greek key motif is thus formed.
Topology diagrams

- Topology diagrams are a way of showing the connectivity of secondary structure, from N- to
C- terminus
- β-strands are shown as arrows and α-helices as rectangles/cylinders



Example

- Human omega-1 receptor
- Mix of alpha helices and beta strands
- Two distinct beta sheets in structure

, 6BBB0333




How can the same motif have different topologies? – e.g. Four helix bundle motif

- Overall 3d arrangement of structural elements may be similar but could be connected in
different ways
- EX: Myohemerythrin and Ferritin both contain a 4-helix bundle 4x alpha helices
- Connection between helices is different




- 4 alpha helices packed against each other
- Topology shows connection of helices from N to C termini
- Each have different topology
- Secondary structure for the same type of motif can be connected differently



Motifs can contain a mixture of secondary structure

For instance

B-a-B motif

- Mix of secondary structure
- 2 PARALLEL beta strands connected by alpha helix -> CROSSOVER (a helix between 2 b
strands)
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