Beyond Pauling-Corey:
Conformation and Peptide Geometry of
Linear Groups in Proteins
Scott Hollingsworth
Dr. P. Andrew Karplus
Department of Biochemistry & Biophysics
Protein Structure

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Ptr Tox A
Proteins carry out the
work in the cell
Each has individual
structure
Structure flows from
function


Structure = Function
My interest in protein
structure…
Model Building
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Ptr ToxA Model
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Sep. 2007 – June 2008
Even with every individual
amino acid conformation
perfect, it was still off
Peptide geometry varies
This summer I got to
investigate this type of
variation
The Peptide
Basic repeating structure of a protein
O
||
(-N-CA-C-)
The Peptide
Basic repeating structure of a protein
O
||
(-N-CA-C-)
Peptide Conformation

Phi & Psi (Torsion Angles)

Phi and psi describe the
conformation of the planar
peptide in regards to other
peptides
Linear Groups

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Series of residues with the same conformation
Textbooks commonly list seven or more
Four most common:
Polyproline
310 Helix
Alpha-Helix
Beta-Sheet
(Parallel and Anti-Parallel)
Objectives

Use current ultra-high resolution structures to determine
the conformations for each common linear group;
determine which do and do not exist

(Peptide conformation)
Vs.
Alpha-Helix

Vs.
310-Helix
Pi-Helix
Determine the geometry (bond lengths and angles) for
each linear group; investigate possible differences

(Peptide geometry)
Protein Geometry Database
(PGD)
Protein Geometry Database
(PGD)
Protein Geometry Database
(PGD)
Methods
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Searches at multiple
resolution cutoffs
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The 1.2A Resolution Data Set
Plot of all residues of 1.2A Res. or better
(30, 972 residues)
Final data at 1.2 Angstrom
(Atomic level) Resolution
Searches were carried out at
3X (three residue long
segments)
Linear
Group
Search
Strategy
Start with
overall
search
Search for
regions with
repeats
Confirmed
Linear
Group
Regions
Beta Region
Alpha Region
L-Alpha Region
Figure 2B. Beta Region at 1.2 Å
ψ
-170
2
2
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
-160
4
4
9
9
4
4
5
5
0
0
0
0
0
0
0
0
1
0
2
0
1
0
0
0
-150
0
0
2
2
4
4
7
5
4
4
0
0
0
0
1
0
2
0
9
0
10
0
0
0
-140
0
0
2
1
2
2
15
15
20
19
4
4
6
4
2
0
3
0
4
0
4
0
1
0
-130
0
0
0
0
1
1
17
17
32
28
24
23
9
8
0
0
2
0
2
0
0
0
0
0
-120
0
0
0
0
0
0
0
0
10
9
21
21
14
12
5
4
0
0
0
0
0
0
0
0
-110
0
0
0
0
0
0
0
0
0
0
1
1
2
2
2
2
0
0
0
0
-100
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
-160
-150
-140
-130
-120
-110
-100
-90
-80
-70
φ
Total
EEE
-60
-50
3D Representation of
Beta Region Map
Beta 3D “Map” at 1.75 A
3D Representation of
Beta Region Map
Mt. Beta Sheet
PP II Hill
Beta 3D “Map” at 1.75 A
Results of Mapping
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Only four of ten textbook linear groups exist in proteins
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Uncommon linear groups
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Alpha Helix (29 %)
Beta Sheet (13 %)
310 Helix (1.14 %)
Polyproline(0.45 %)
L-Alpha (0.003 %)
No other linear groups exist
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2.2 Ribbon, Pi Helix, Epsilon, Zeta, Gamma...
Commonly
Cited
Linear
Groups
Alpha Helix
L-Alpha Helix
310 Helix
L-310 Helix*
Pi - Helix
Parallel Beta Sheet
Anti-parallel Beta Sheet
Polyproline II
Polyglycine II
Collagen
Epsilon*
Gamma*
Gamma Prime (2.2r)
180
C
↑↑
90
2
αL
0
3
α
π
-90
-180
-180
* Not Shown
II
↑↓
-90
0
90
180
Adapted from: Schultz and Schirmer (1979), Kyte (1995), Lesk (2001), Voet et
al. (2004), Garrett and Grisham (2005), and Voet et al. (2008)
Confirmed
Linear
Groups
180
90
Beta Sheet
αL
0
310
Polyproline
310Helix
Alpha Helix
(R & L)
α
-90
-180
-180
-90
0
90
180
Comparison of Phi/Psi

Linear
Group
Old
Conformation
Updated
Conformation
Alpha Helix
(-57, -47)
(-62.5, -42.6)
310 Helix
(-49, -26)
(-62.5, -21.7)
Parallel Beta
(-119, 113)
(116.1, 129.1)
Anti-Parallel Beta
(-139, 135)
(116.1, 129.1)
Polyproline
(-79, 150)
(-65.4, 145.0)
Significant differences between textbook and
true values

Old data separated Beta Sheet into two variations, updated
data shows that there is little conformational difference
between the two
Peptide Geometry
Bond angles show dependence on
conformation
Bond lengths did not show significant
variation
 There is no single correct peptide
geometry
108.4
Beta I
108.8
Beta II

110.3
PP II
110.9
Alpha
Helix
112.1
310-Helix
106
108
110
112
114
116

N-Cα-C
Conclusions

Only four true linear groups exist
Alpha Helix, 310 Helix, Beta Sheet, Polyproline
 All other proposed linear groups (ex. Pi-helix), do
not exist in proteins
 Significant differences between textbook angles and
true values

Vs.
Alpha-Helix
Vs.
310-Helix
Pi-Helix
Conclusions

Bond angles do show dependence on
conformation
Angles vary anywhere from 1.4 to 3.7 degrees across
the four linear groups
 Accounting for this variation would allow for more
accurate structures

Acknowledgements
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HHMI
Dr. P. Andrew Karplus
Donnie Berkholz
Dr. Lynda Ciuffetti
Dr. Weng-Keen Wong
Dr. Kevin Ahern
Manuscript in progress
The “World” of Proteins
Hollingsworth, S.A., Berkholtz, D.S., Karplus, P.A. 2008. Beyond Pauling-Corey:
Conformation of linear groups in proteins at ultra high resolution. (In Progress)