Struttura primaria
Struttura secondaria
(alfa-elica, filamento beta, turn)
Struttura supersecondaria
(motivi strutturali)
All alpha
All beta
Alpha and beta
Alpha + beta
All- topologies
The lone helix
There are a number of examples of small proteins (or peptides) which
consist of little more than a single helix. A striking example is
alamethicin, a transmembrane voltage gated ion channel, acting as a
peptide antibiotic.
The helix-turn-helix motif
The simplest packing arrangement of a domain of two helices is for them to lie
antiparallel, connected by a short loop. This constitutes the structure of the small (63
residue) RNA-binding protein Rop , which is found in certain plasmids (small circular
molecules of double-stranded DNA occurring in bacteria and yeast) and involved in
their replication. There is a slight twist in the arrangement as shown.
Catene laterali idrofile
Catene laterali idrofobe
Cytochrome c1
Fascio di 4 eliche antiparallele
2 coppie di eliche parallele
unite in modo antiparallelo
 domains which bind DNA
A three-helix bundle forms the basis of a DNA-binding domain which
occurs in a number of proteins
Strutture “all alpha”
elica solitaria
Fascio di 4 eliche
Globine (fascio di 8 eliche)
Domini ad alfa elica di grandi dimensioni
All- topologies
The Greek Key topology
The Greek Key topology, named after a pattern that was common on
Greek pottery, is shown below. Three up-and-down -strands connected
by hairpins are followed by a longer connection to the fourth strand,
which lies adjacent to the first.
Ipotetica modalità di
ripiegamento di una struttura a
forcina per formare la struttura a
chiave greca. I filamenti  2 e 3
si ripiegano sugli altri due in
modo che il filamento 2 viene ad
essere allineato e antiparallelo al
filamento 1.
Gamma-crystallin has two domains each of which is an eight- stranded
-barrel-type structure composed of two Greek keys. In fact, the
structure is more accurately described as consisting of two -sheets, one
consisting of strands 2,1,4,7 (white) and the other of strands 6,5,8,3 (red)
as indicated in the diagram.
Aligned and orthogonal  sandwiches
Diagram of this -sheet arrangement in the Lipocalin family, which
binds small molecules between the sheets of the sandwich.
 barrels
Strutture alfa/beta
/ topologies
The most regular and common domain structures consist of repeating - supersecondary units, such that the outer layer of the structure is
composed of  helices packing against a central core of parallel -sheets.
These folds are called / , or wound  .
Many enzymes, including all those involved in glycolysis , are /
structures. Most / proteins are cytosolic.
The -- is always right-handed. In / structures, there is a repetition
of this arrangement, giving a ---.....etc sequence. The  strands are
parallel and hydrogen bonded to each other, while the  helices are all
parallel to each other, and are antiparallel to the strands. Thus the helices
form a layer packing against the sheet.
The ---- subunit, often present in nucleotide-binding proteins, is
named the Rossman Fold, after Michael Rossman (Rao and
Beta-alfa-beta destrorsa
Beta-alfa-beta sinistrorsa
Elica di collegamento
Alfa-eliche sul medesimo
piano del foglietto beta
Alfa-eliche su piani
opposti del foglietto beta
/ barrels
Consider a sequence of eight - motifs
If the first strand hydrogen bonds to the last, then the structure closes on
itself forming a barrel-like structure.
Enzima triosofosfato isomerasi
Struttura a “TIM barrel”
Enzima lattato deidrogenasi
Rossman Fold
In tutte le strutture / a botte il sito attivo si trova in una
tasca formata dalle regioni loop che collegano le estremità
carbossiliche dei filamenti beta con le adiacenti alfa eliche.
Nei domini con struttura / aperta ruotata il sito attivo si trova in una
fessura localizzata esternamente all’estremità carbossilica del filamenti
. Questa fessura è formata da due regioni loop adiacenti che collegano
i due filamenti con  eliche presenti su facce opposte del foglietto 
Adenilato chinasi
Punti di inversione topologica (topological switch points)
Strutture alfa/beta
I) TIM barrel
II) a)Struttura / aperta e ruotata (di tipo parallelo o misto)
- b) Rossmann fold
III) / horseshoe (ferro di cavallo)
Alpha+Beta Topologies
Structural Classification of Proteins (SCOP)
Authors. Alexey G. Murzin, Loredana Lo Conte, Bartlett G. Ailey, Steven E. Brenner, Tim J. P. Hubbard, and Cyrus Chothia.
Reference: Murzin A. G., Brenner S. E., Hubbard T., Chothia C. (1995). SCOP: a structural classification of proteins database for
the investigation of sequences and structures. J. Mol. Biol. 247, 536-540.
1.All alpha proteins (151)
2.All beta proteins (111)
3.Alpha and beta proteins (a/b) (117)
Mainly parallel beta sheets (beta-alpha-beta units)
4.Alpha and beta proteins (a+b) (212)
Mainly antiparallel beta sheets (segregated alpha and beta regions)
5.Multi-domain proteins (alpha and beta) (39)
Folds consisting of two or more domains belonging to different classes
6.Membrane and cell surface proteins and peptides (12)
Does not include proteins in the immune system
7.Small proteins (59)
Usually dominated by metal ligand, heme, and/or disulfide bridges
8.Coiled coil proteins (5)
Not a true class
9.Low resolution protein structures (17)
Not a true class
10.Peptides (95)
Peptides and fragments. Not a true class
11.Designed proteins (36)
Experimental structures of proteins with essentially non-natural sequences. Not a true class
Membrane protein topology
Paradosso di Levinthal
• Proteina di 100 residui
• Due gradi di liberta’ torsionali/residuo (phi,psi)
• 3 conformazioni accessibili per ogni grado di
liberta’ torsionale
• 􀃆 32x100 possibili conformazioni
• @ 1013 conformazioni esplorate/sec
• Tempo richiesto per esplorare tutte le
conformazioni: t = 20 x 109 anni !
• Le proteine si devono ripiegare seguendo un
cammino definito, caratterizzato da conformazioni
via via piu’ stabili (diminuizione di G)