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Handedness of β-α-β motif
Presented by Chen Zhang
2006-12-04
Pre-word
• My original topic is about domain prediction
• I did a lot but it turned out not fruitful
enough
• Just changed to this project in the morning
• Sorry that
• It would not be long
• It would not be comprehensive
• May have error ..
• New project
• Survey & explain β-α-β motif handedness
• Possible extension
• Survey & research on twist/chirality effects
Background of β-α-β motif (Prof. Li)
This is called the β-α-β motif.
Occurs in almost all proteins with
parallel β sheets.
Left: right-handed connection, via a righthanded α helix. All β-α-β motifs are
connected this way.
Right: Theoretically, left-handed connection
is possible (below the plane). But never
occur.
No convincing argument explaining this.
Possible project: survey and explain.
The Question
• Why right-handed for almost all β-α-β ?
• Intuition: Lower energy? Yes [2]
• Two principles have a dominating influence on
how secondary structures associate. [1]
• Residues that become buried in the interior of a protein
close-pack: they occupy a volume similar to that which
they occupy in crystals of their amino acid (3, 4).
• Associated secondary structures retain a conformation
close to the minimum free energy conformation of the
isolated secondary structures.
How lower energy is got?
• What happens internally?
• Right handed twist of β sheet [3]
• Sheets themselves have lower free energy
• Twist affects structure, shows handedness
preference
• Protein folding path way [4]
Right handed twist of β sheet [3]
• Why twist?
• A sheet with a right-hand twist when viewed
along the polypeptide chain direction has a
lower free energy than sheets which are
straight or have a left-hand twist.
• We can best consider the conformation of β
sheets by reference to the Ramachandran
diagram.
Right handed twist has lower energy
• The free energy of an assembly, G, is related to
enthalpy, H, and entropy, S, by the equation G = H TS. The entropy is given by X = k In Ω, where Ω is
the number of a priori equally probable
macromolecular states of the assembly.
• All Φ, Ψ values within the normally allowed region
of the Ramachandran plot in previous Figure
represent equally probable macromolecular states.
• Therefore, polypeptide chains with a right-hand
twist will have a greater entropy than those which
have a left-hand twist or are straight.
Right handed twist has lower energy
• Thus, from theoretical calculation and
empirical observation we can say that the
absolute minimum energy (enthalpy)
conformation for extended polypeptide
chains occurs to the right of the line n = 2
and it will therefore have a right-hand twist.
[3]
• This is mainly due to a left-hand twist of the
polypeptide chain moving the carbonyl
group too near to the residue side chains as
shown in the following Figure.
Right handed twist of β sheet
Due to Right handed twist of β
sheet
• If the unit had no right-handed preference,
the probability of observing such a
distribution by chance is very small. [2]
• How is the twisted β sheet influence the
handedness of crossover connection?
Due to Right handed twist of β
sheet
• As shown that a right-handed connection in
the β x β unit allows a direct path for the
chain to connect the strands
• In contrast, a left-handed one would require
the chain to negotiate a more complex path
to avoid steric interactions with the ends of
the strands.
Protein folding path way
• Proteins fold through a series of intermediate states
called a pathway. [11]
• The helix would tend to form at least as early in the
folding process as the strands. there can be a smooth
transition to a right-handed loop with the helix
unwinding slightly at the ends.
• In this case, the preference for righthandedness depends
on the righthandedness of the a-helix, combined with
the fact that it is much more likely for the backbone to
leave both ends of the helix in a fairly smooth
continuous direction than for both ends to reverse
sharply at that point. [4]
Protein folding path way
• The shown folding path way folds in a
one-step process of bringing together the
two β strands. It is a two-step folding
process in which first the intervening
chain folds against one β strand, and then
the second β strand folds down next to
the first.
• A characteristic which enables the shown
pathway to prejudice handedness is the
condition that the ends of the folding
section of chain are held approximately in
place over very short time spans by the
rest of the protein mass.
Concluding Remark
• It may be that the nearly compulsory righthandedness of crossover-connection loops is
a combined result of several contributing
causes as we mentioned but not limited to,
however, each of those happens to prejudice
the result in the same direction.
Future work
• Do more extensive survey and try to find
better explanations to the problem
• Do extended survey about twist/chirality
• Main issues that I try to find in the extended
survey will be:
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Twist and handedness affect structure
What other effects could they have?
How to better consider them in prediction?
…
Reference
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[1] Chothia et al., Structure of proteins: Packing of a-helices and
pleated sheets
[2] Sternburg et al., On the Conformation of Proteins: The
Handedness of the β Strand-α Helix-β Strand Unit
[3] Chothia, Conformation of Twisted β-pleated Sheets in Proteins
[4] Richardson, Handedness of crossover connections in β sheets
[5] Braun, Representation of Short and Long-range Handedness in
Protein Structures by Signed Distance Maps
[6] Scheeff et al., Fundamentals of protein structure.
[7] Weatherford et al, Confirmations of twisted parallel β–sheets and
the origin of chirality in protein structures.
[8] Levitt, Structural patterns in globular proteins
[9] Kuntz, An Approach to the Tertiary Structure of Globular
Proteins
[10] Efimov, Structural Trees for Protein Superfamilies
[11] Bystroff et al., Modeling Protein Folding Pathways
[12] Skolnick, A unified approach to the predictiion of protein
structure and function