Richard C.

Garratt
Christine A. Orengo

The “periodic table” of

proteins illustrates the beauty,
diversity, and complexity of
proteins in one place. It is a re-
markable teaching and learning tool.
(Donald Voet, author of “Biochemistry”)

The ideal tool to understand and to

teach the principles of protein structure,
and beautifully designed. I wholeheartedly
recommend it.
(Robert Huber, Nobel Prize in Chemistry 1988)
The columns of the table are based α-Proteins β-Proteins
on domain architectures as defined Orthogonal Bundle Up-down Bundle α Horseshoe α Solenoid α/α Barrel β - Ribbon/Sheet/Roll β - Barrel β - Sandwich
by the CATH hierarchical classifica- 12.98% 3.63% 2.03% < 0.01% 0.17% 3.16% 3.68% 4.90%
tion. Each cell provides information 1ois 73 1u5p 106 1bd8 207 1ppr 156 1fce 369 1www 101 1khi 91 1k5n 112
001 (19) A01 (16) 000 (80) M01 (1) 001 (58) V00 (13) A02 (27) A02 (24)
on an interesting fold group within
that architecture and highlights a par-
ticular structural domain from that
group. The first row of each column
typically contains the most basic fold
group for that architecture followed
EAP EAP EAP EAP EAP EAP EAP EAP
by fold groups with more complex 1.10.10 S(2)H(2)SH 1.20.58 H(4) 1.25.40 H(10) 1.40.10 H(8) 1.50.10 H(6)S(3)H(2)S(3)H(4)S(5)H(2)S(2)H 2.10.90 HS(11) 2.40.50 S(4)HS(3) 2.60.40 S(9)

structures. The population given as Arc repressor 3-Helix bundle α5 Horseshoe α Solenoid (α/α)6 Barrel Cystine knot OB fold (β5) Immunoglobulin-like
a percentage for each architecture is Ankyrin-like repeat
calculated from the 527 genomes 1ckk 93 1e85 125 1lrv 481 2bml 115 1gm6 139 1g6e 87
A01 (34) A00 (24) 000 (145) A00 (18) A00 (25) A00 (4)
present in Gene3D version 6.0.
Known functions have been auto-
matically assigned to one of eight cat-
egories in the Gene Ontology (GO)
molecular function classification (see
legend). These categories are repre-
EAP EAP EAP EAP EAP EAP
sented as a coloured octagon around 1.10.238 H(4) 1.20.120 H(6) 1.25.10 H(10) 2.10.270 S(12) 2.40.128 S(12)HS 2.60.20 S(2)HS(7)
the structure and are based on a clas- EF-hand 4-Helix bundle α9 Horseshoe Left-handed (ββ)3 solenoid Lipocalin-like (β8) γβ-Crystallin Greek key
sification scheme devised by Christos Leucine rich repeat variant
Ouzounis. For each fold group, the 1mbn 147 1ap9 236 1lsh 481 1lsh 98 1emg 223 2stv 194
000 (9) 000 (46) A02 (145) A03 A00 (5) 000 (49)
GO categories are those identified for
all structures within that fold group,
excluding electronically inferred an-
notations, as well as all annotated se-
quence homologues to those structu-
res (at 60% sequence identity, 80%
EAP EAP EAP EAP EAP EAP
overlap of the larger domain) in 1.10.490 H(9) 1.20.1070 H(12) 1.25.10 H(16) 2.20.50 S(7)HS(2) 2.40.155 S(4)HS(9) 2.60.120 HS(5)H(2)S(6)
Gene3D. Functions are assigned Globin 7 TM bundle α10 Horseshoe Single open sheet Green fluorescent protein Jelly roll
based on the whole structure to which (β11)
the domain belongs and may there- 1a28 238 1wpg 418 1qsa 363 1h64 74 2fgq 282 3enr 194
A00 (16) B02 (8) A01 (47) A00 (19) X00 (75) B00 (49)
fore not always represent a specific
functional attribute of that domain.
A white octagon tile means that no
proteins in that fold group have that
function. The incremental filling of
the tile (by 1/4, 1/2, 3/4, 1/1) indicates
EAP EAP EAP EAP EAP EAP
the presence of the respective func- 1.10.565 H(4)S(2)H(3)SH(6)S 1.20.1110 H(14) 1.25.20 H(26) 2.30.30 HS(8) 2.40.160 S(9)HS(14) 2.60.120 S(18)
tions in the fold group and their rela- α8 Orthogonal α10 Bundle α12 Horseshoe β5 α1 roll (SH3-like) Porin (β16) Concanavalin A-like
tive importance (i.e. up to 25 / 50 /
75 / 100% of all proteins in that fold 1s4b 375 1jb0 739 1u6g 481 1t77 119 1kmo 461
group have that function). For the P02 A00 C00 (145) A01 (24) A02 (57)

fibrous proteins the functional map-

ping is simply that of the particular
structure shown and its 60% sequen-
ce identity homologues. A completely
blank octagon reflects the fact that
EAP EAP EAP EAP EAP
currently no function can be auto- 1.20.1130 SH(3)S(3)H(2)SH(15)
1.10.1370 HS(3)H(18) S(2)H(3)S(2)H(7) 1.25.10 H(60)S(2)H(7) 2.30.29 S(5)H(2)S(5)H 2.40.170 S(5)HS(31)
matically mapped to that fold, but not
α13 Orthogonal α12 Bundle Superhelical horseshoe PH domain Maltoporin (β22)
necessarily that no known function
exists.
 α/β-Proteins
β - Propeller β - Helices β - Prism β -Trefoil β - Clam 3-Layer β - Sandwich α/β Roll/Super Roll 2-Layer Sandwich (αβ) 3-Layer Sandwich (αβα) 3-Layer Sandwich (ββα)
1.29% 0.59% 0.03% 0.07% 0.04% 0.13% 2.71% 15.26% 33.96% 1.66%
1itv 197 1k7i 230 1ouw 142 1ybi 143 4bcl 353 1tg7 181 1aar 97 1ay7 88 4fxn 206 1bht 85
A00 (8) A01 (11) A00 (14) A01 (21) 000 (5) A02 A00 (26) B00 (2) 000 (80) B01 (12)

EAP EAP EAP EAP EAP EAP EAP EAP EAP EAP
2.110.10 S(4)HS(9)HS(4) 2.150.10 HS(19) 2.100.10 S(14) 2.80.10 S(13)H 2.50.10 S(10)HS(2)H(4)S(4)HS(9) 2.102.20 S(18)H 3.10.20 S(2)HS(3) 3.30.370 SH(2)SH(2)S 3.40.50 SHS(2)HS(3)H 3.50.4 S(3)HS(4)

4-Bladed propeller Right-handed β2 helix Parallel β prism β-Trefoil β-Clam 3-Layer β-sandwich UB Roll α3 β3 -Sandwich Flavodoxin β2 β5 α2 -Sandwich

1tl2 319 1p9h 230 1b2p 109 1mol 110 1cc8 106 1t2d 206 1jke 161
A00 (14) A00 (11) A00 (3) A00 (22) A00 (27) A01 (80) A00 (20)
Legend
Domain ID for reference structure
(PDB code, chain ID, domain number)

EAP EAP EAP 1ybi 143 Average length EAP EAP EAP EAP
2.115.10 2.150.10 2.90.10 3.10.450 3.30.70 3.40.50 3.50.80
5-Bladed propeller
S(2)HS(18)

Left-handed β2 helix
S(20)H

Orthogonal β prism
S(11)
A01 3 (21) (in residues) and α1 β5 Roll
SHS(7)

αβ-Plait (α2β4)
SHS(2)HS

Rossmann fold
SH(3)S(2)HS(2) S(4)HS(3)HS(3)

β3β5α2-Sandwich
standard devia-
1npe 360 1ee6 344 1 Binding
2 4 tion for the fold 1lg7 163 1lc0 169 1hv8 206 1fec 196
A00 (49) A00 (123) A00 A02 (42) A01 (80) A02 (68)
2 Nucleic acid bin- group.
ding/translation
regulator activity 1 5
3 Catalytic activity
4 Transporter
EAP EAP activity EAP EAP EAP EAP
2.120.10 S(25) 2.160.20 S(28) Taxonomy 3.10.460 S(2)H(2)S(5)HS(2) 3.30.360 HSH(3)S(5)H 3.40.50 H(2)SH(7)S 3.50.50 HSHSHS(5)

6-Bladed propeller Right-handed β3 helix

5 Enzyme regulator 8 6 (E=eukarya, α4 β4 Roll α3β5 -Sandwich P-loop hydrolase FAD/NAD(P) binding
activity
6 Structural molecule 7 EAP A=archaea,
1k3i 368 1hm9 180 1ewf 180 1k5n 179 1qmu 222 1b7y 214
A02 (48) A02 (38) activity P=bacteria) A01 A01 (5) A01 (68) B03
2.80.10 S(13)H
Red indicates the
7 Signal transducer
presence of the
β -Trefoil
activity
8 Motor activity domain in that
lineage.
yellow background
EAP EAP indicates top ten most Fold name EAP EAP EAP EAP
2.130.10 2.160.10 3.15.10 HS(14)H(3) 3.30.500 S(3)H(3)S(4)H(3) 3.40.630 HS(3)H(2)SH(2)S(2)H(2)SH(4) 3.50.40 S(3)H(2)S(8)H(3)S(2)
S(31) S(30)
highly populated fold CATH code Secondary structure string Class I MHC
7-Bladed propeller Left-handed β3 helix Super-roll α5 β7 α3 -Sandwich β5β4α3 -Sandwich
groups (superfolds) for fold group (H=helix, S=strand) (α2 β8 -Sandwich)
1qks 475 1t9i 134
A02 (52) A00 (22)

EAP EAP
2.140.10 HS(36)H 3.10.28 HS(5)H(5)

8-Bladed propeller Inside-out roll

 Knots & Fibres
3-Layer Sandwich (βαβ) 4-Layer Sandwich (αββα) α/β Horseshoe α/β Barrel Miscellaneous α-Helical Fibrous Other Fibrous Knots
0.03% 1.43% 0.39% 4.34% 0.17%
1dl5 115 1txo 251 1fs2 275 7odc 313 1plq 258 2b9c 278 1cag 88 1mxi 160 Compiled by
A02 B00 (29) A00 (93) A02 (70) 000 (21) A00 (13) Richard C. Garratt
(University of São Paulo, Brazil)
and
Christine A. Orengo
(University College London, UK)

EAP EAP EAP EAP EAP EAP EAP EAP Designed by

3.55.20 HSHS(4)HS(2) 3.60.40 S(3)H(2)S(4)H(2)S(2)H(3)S 3.80.10 H(4)SH(6)S(2)HS 3.20.20 HSHSHSHSHSHSHSHS 3.70.10 SHS(5)HS(4)HS(5)HS(3) N/A H(6) N/A SSHH 3.40.1280 SH(3)S(2)HSH

β9 Horseshoe Adam Design

β2α2β5 -Sandwich α2 β5β5α2 -Sandwich TIM barrel α/β Box Left-handed coiled coil Collagen-like 31 Trefoil knot
Leucine rich repeat (Weinheim, Germany)
1jw3 128 1b25 209 2ca6 275 1i7e 246 1g6s 210 1sjj 1726 1l3w 540 1xd3 217
A00 (12) A01 A00 (93) A00 (19) A01 (7) A00 (9) The collaboration of Alison Cuff,
Ian Sillitoe, Humberto Pereira and
Janet Thornton is gratefully acknow-
ledged.
With a few exceptions, all protein
structures have been taken from the
EAP EAP EAP EAP EAP EAP EAP EAP CATH database (www.cathdb.info).
3.55.10 S(2)H(3)SH(3)S(4) 3.60.9 S(2)H(2)S(3)HS(3)HSHS(2)HS 3.80.10 S(2)H(2)S(2)HS(10) 3.20.90 HS(7)HS(2)HS(7)H 3.65.10 S(3)H(2)SHS(3)HS(6) N/A H(38) N/A S(15)HS(25) 3.40.532 HS(2)H(5)S(3)HS

β4 α2 β3 -Sandwich α2 β6 β6 α1 -Sandwich β12 Horseshoe Tubby fold α/β Prism Spectrin-like 3-helix bundle Cadherin-like 41 (Figure-of-eight) knot
Leucine rich repeat
1hw7 202 1xff 225 2bex 275 1qu7 448 1yve 152
A01 (31) A00 (35) A00 (93) l02 (76)

EAP EAP EAP EAP EAP

3.55.30 S(2)H(2)S(3)HS(2)HS(2) 3.60.20 SHS(2)HS(3)H(3)S(9) 3.80.10 SH(19)S N/A H(9) 1.10.1040 H(22)

Hsp33 domain (β4α3β5) α2 β6 β8 α2 -Sandwich β17 Horseshoe Antiparallel 4-helix bundle 52 Knot
Leucine rich repeat
1vzy 202 1k0e 467 1av1 804
A01 (31) A00 (47)

EAP EAP EAP

3.55.30 S(2)H(2)S(3)HS(4)H(3)S(2) 3.60.120 SHS(22)H(2)S(4)H(2) N/A H(7)
All rights reserved, including those
Hsp33 domain (β5 α3 β5 α3) Orthogonal sandwich Antiparallel 4-helix closed of translation into other languages.
bundle Reproduction (by photoprinting,
microfilm, or any other means) and
translation into machine language
not permitted.

© 2008 WILEY-VCH Verlag

GmbH & Co. KGaA,
Weinheim
 Basic topologies of secondary structure
β - Hairpin N-type Greek key
β - Meander C-type Greek key α-Solenoid
The β-hairpin and the
β-meander are exam-
ples of the simplest
type of up-and-down
antiparallel β-sheet
topologies. The latter
has an additional strand
Ig domain
(yellow) with respect to
the former. They can The Ig fold is one of
be observed in innumer- the most well-known of
able examples of β-struc- all protein structures.
tures shown in the main An Ig constant domain,
table. as shown here, has an
N-type Greek key em-
bedded within it (shown
in green).
in nucleotide binding
proteins. It is composed
of two topologically
identical and pseudo-
symmetrically related
substructures, which
are shown in different
Rossmann fold colours. The term
Rossmann fold is also
The Rossmann fold
occasionally used to
was first described by
refer to such substruc-
Michael Rossmann as
tures. Several examples
a motif observed in lac-
can be seen in the main
tate dehydrogenase.
table.
It is common in α/β
proteins with open β-
sheets and particularly
The jelly roll, α-solenoid
and αβ-plait topologies
are surprisingly similar
despite their different
secondary structures.
All are based on a giant
hairpin which is subse-
Jelly roll
quently rolled up to
form a compact domain
in which the secondary
structures form two lay-
ers (the β-sheets in the
case of the jelly roll).
The latter is probably
the most well-known of
the three folds and
takes its name from the
topology diagram of its
β-strands, which resem-
bles a slice of a jelly roll
(Swiss roll).
αβ - Plait
The kringle takes its
name from the topolo-
gy imposed by its three
disulphide bridges,
which in two dimensi-
ons resembles a Danish
pastry of the same name.
Kringle It is a common modu-
lar element in proteins
of the coagulation path-
ways.
Important structural motifs
The helix-turn-helix
and EF-hand motifs are
both characterized by
two orthogonal α-helices.
The former is a specific
example of an α/α corner
and is found in DNA
HTH motif binding proteins, where
the second (recognition)
helix inserts into the
major groove. The EF-
hand is observed in Ca2+
binding proteins, where
the Ca2+ is bound by a
loop between the two
EF hand helices.
Both the leucine zipper
and the helix-loop-helix
are dimerization motifs.
In the former case this
occurs via the formation
of a classical left-handed
coiled coil, with leucines
Leucine zipper at every 7th position (the
d position of the coiled
coil). In the case of the
HLH, the two helices of
the motif come together
with those of the second
monomer to form a 4-he-
lix bundle.
HLH motif
right-handed left-handed
Right handed βαβ βββ motif
Most connections between
parallel β-strands are right-
handed, but exceptions
are to be seen in the left-
handed β-helices of the
main table. The βαββ
motif includes an addi-
βαββ motif tional intervening anti-
parallel strand.
The Greek key and the in-
terdigitated β-arches are
two of the most commonly
observed motifs (or sub-
structures) in β-proteins.
The former is predominan-
tly observed at the edges of
Greek key antiparallel β-sheets where
the motif is often divided
between two such sheets.
The latter has been descri-
bed as the most common
sub-structure observed in
β-sandwiches.
2 β - Arches
Zinc fingers are metal
binding motifs involved
in DNA recognition. They
differ in their Zn2+ ligands,
3D structures and DNA
binding modes. The exam-
ple shown is a ‘classical’
Zinc finger Zinc finger involving two
His and two Cys ligands.
The P-loop is a glycine rich
motif involved in nucleotide
binding, where it interacts
directly with the α and β
phosphate moieties.
P- loop
The Leucine rich repeat
(LRR) is characterized by
a sequence motif which
typically contains 6 leuci-
nes. They form a structural
motif of a β-strand, α-helix
and connecting loop.
Leucine rich repeat Several examples of pro-
teins, containing different
numbers of repeats, can
be seen in the αβ-horses-
hoes of the main table.
 Oligomeric Proteins
Legend
PDB code for Number Highest Order Rotation Axis
reference structure of subunits
1 2 3 4 5 6 7 >7

1aqd 2 1wrp 2 1rtm 3 1bl8 4 1lts 5 1do0 6 1i8f 7 1lgh 16

1qtj 16
3
2 4

C1 1 C2 2 C3 3 C4 4 C5 5 C6 6 C7 7 C8 8
1 5 HLA class II Trp repressor C-typeArc
mannose binding
repressor Potassium channel HeatArc
labile enterotoxin
repressor HslU ATPase SmAP LHC Arc
II Rhodospirillium
repressor
protein (B subunit) molischianum
3hvt 2 2pol 2 1cd5 6 1cuk 4 1msl 5 1g8y 6 7ahl 7 1nkz 18

8 6
7
D8 822
SAP from horseshoe crab C1 1 C2
Bacterial polymerase
2 D3
Glucosamine 6-P
32 C4
RUVA (DNA
4 C5 5 C6
Helicase
6 C7 7 C9 9
HIV reverse transcriptase Arc repressor Arc repressor Arc repressor Mechanosensitive channel ArcRepA of plasmid
repressor Alpha-hemolysin LHC
ArcII repressor
Rhodopseu-
III β subunit (E. coli) deaminase recombination protein) RSF 1010 domonas acidophila
Protein name 1hzh 4 3phv 2 1raa 12 1dhn 8 1gtp 10 1y12 6 1grl 14 1wap 11
Point group Point group
symmetry symmetry
(Schoenflies (International
nomenclature) nomenclature)

1 Multiple sites, cross-linking,

membrane association C1 1 C2 2 D3 32 D4 422 D5 52 C6 6 D7 72 C11 11
IgG HIV protease Aspartate transcarb-
Arc repressor 7, 8-Dihydroneopterin
Arc repressor GTP cyclohydrolase I Protein secretion
Arc repressor GroEL TRP
ArcRNA binding
repressor
2 Cooperativity/allosterism amoylase aldolase apparatus (HCP1) attenuation protein (TRAP)
3 Cavities, channels and pores 2aai 2 4hhb 4 1dps 12 1a6d 16 1rvv 60 1f52 12 1pma 28 1qtj 16
4 Functional (active) site formation
5 Size and stability
6 Economy of genetic material
7 “Rulers” (exact separation
between binding sites)
8 Multiple functions (in hetero- C1 1 C2 2 T 23 D4 422 I 532 D6 622 D7 72 D8 822
oligomers) Ricin Human haemoglobin DNA binding protein Dps Thermosome lcosahedral lumazine
Arc repressor Glutamine synthase Proteasome SAP from horseshoe crab
synthase (B. subtilis)

Yellow background indicates 4pfk 4 3pcg 24 2fha 24 1stm 60 1g3k 24

dihedral symmetry
ISBN 978-3-527-31963-3
Gray background indicates cubic/
icosahedral symmetry

D2 222 T 23 O 432 I 532 D6 622

Phosphofructokinase Protocatechuate
Arc repressor Ferritin Satellite panicum
Arc repressor HsIUV
ArcATP dependent
repressor
3,4-dioxygenase mosaic virus protease