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Struttura primaria: sequenza lineare degli aminoacidi
Struttura secondaria: disposizione spaziale degli atomi dello
scheletro polipeptidico regolare e ripetitiva in residui
adiacenti
Struttura terziaria: ogni ulteriore ripiegamento della catena
polipeptidica; struttura tridimensionale globale del
polipeptide
Struttura quaternaria: disposizione spaziale delle subunità di
una proteina oligomerica
Protein length distribution
H.sapiens
Average protein
length : 453 +/- 512
amino acid residues
Size range:
3 - 34350
amino acid residues
Protein length distribution
E.coli K12
Average protein length :
316 +/- 215 amino acid
residues
Size range:
14 - 2358
amino acid residues
phi
CA—C—N—CA—C—N
omega
psi
n: aminoacido in esame;
n-1: aminoacido precedente;
n+1: aminoacido seguente
CA: carbonio alfa; C: carbonio carbonilico; N: azoto amidico
Phi: angolo di rotazione tra carbonio alfa e azoto amidico; angolo diedro
tra il piano formato dagli atomi Cn-1, Nn, CAn ed il piano Nn, CAn, Cn.
Psi: angolo di rotazione tra carbonio alfa e carbonio carbonilico; angolo
diedro tra il piano formato dagli atomi Nn, CAn, Cn ed il piano CAn, Cn,
Nn+1.
Omega: angolo di rotazione del legame peptidico = 180°
Ramachandran plot
psi
phi
-elica
Space-filling model
-elica
In giallo:
Catene
laterali
The structure repeats itself every 5.4 Å along the helix axis, i.e. we say
that the -helix has a pitch of 5.4 Å.
-helices have 3.6 amino acid residues per turn, i.e. a helix 36 amino
acids long would form 10 turns.
The separation of residues along the helix axis is 5.4/3.6 or 1.5 Å, i.e. the
-helix has a rise per residue of 1.5 Å.
1.Every main chain C=O and N-H group is hydrogen-bonded to a
peptide bond 4 residues away (i.e. On to Nn+4). This gives a very
regular, stable arrangement.
2.The peptide planes are roughly parallel with the helix axis and the
dipoles within the helix are aligned, i.e. all C=O groups point in the
same direction and all N-H groups point the other way. Side chains
point outward from helix axis and are generally oriented towards its
amino-terminal end.
Distortions of -helices.
The majority of -helices in globular proteins are curved or distorted somewhat
compared with the standard Pauling-Corey model. These distortions arise from several
factors including:
1.The packing of buried helices against other secondary structure elements in the
core of the protein.
2.Proline residues induce distortions of around 20 degrees in the direction of the
helix axis. This is because proline cannot form a regular -helix due to steric
hindrance arising from its cyclic side chain which also blocks the main chain N
atom and chemically prevents it forming a hydrogen bond. Janet Thornton has
shown that proline causes two H-bonds in the helix to be broken since the NH
group of the following residue is also prevented from forming a good hydrogen
bond. Helices containing proline are usually long perhaps because shorter helices
would be destabilised by the presence of a proline residue too much. Proline occurs
more commonly in extended regions of polypeptide.
3.Solvent. Exposed helices are often bent away from the solvent region. This is
because the exposed C=O groups tend to point towards solvent to maximise their
H-bonding capacity, i.e. tend to form H-bonds to solvent as well as N-H groups.
This gives rise to a bend in the helix axis.
L'enantiomero L è classificato tra i 20 amminoacidi ordinari in quanto
la prolina entra nella composizione di molte catene polipeptidiche. Tra
essi, è l'unica ad avere il gruppo amminico secondario, dato che il suo
gruppo laterale si chiude sull'atomo di azoto formando una struttura
ciclica. Per questo motivo, chimicamente, la prolina è in realtà un
imminoacido, non un amminoacido.
Essendo l'unico amminoacido il cui gruppo amminico è secondario,
non sviluppa per reazione con la ninidrina il colore viola tipico degli
altri amminoacidi, ma presenta una colorazione giallo/rossa.
Most peptide bonds overwhelmingly adopt the trans isomer (typically 99.9%
under unstrained conditions), chiefly because the amide hydrogen (trans
isomer) offers less steric repulsion to the preceding Cα atom than does the
following Cα atom (cis isomer). By contrast, the cis and trans isomers of the
X-Pro peptide bond (where X represents any amino acid) both experience
steric clashes with the neighboring substitution and are nearly equal
energetically. Hence, the fraction of X-Pro peptide bonds in the cis isomer
under unstrained conditions ranges from 10-40%; the fraction depends
slightly on the preceding amino acid, with aromatic residues favoring the cis
isomer slightly. From a kinetic standpoint, cis-trans proline isomerization is
a very slow process that can impede the progress of protein folding by
trapping one or more proline residues crucial for folding in the non-native
isomer, especially when the native protein requires the cis isomer. This is
because proline residues are exclusively synthesized in the ribosome as the
trans isomer form. All organisms possess prolyl isomerase enzymes to
catalyze this isomerization, and some bacteria have specialized prolyl
isomerases associated with the ribosome. However, not all prolines are
essential for folding, and protein folding may proceed at a normal rate
despite having non-native conformers of many X-Pro peptide bonds.
Prolil-isomerasi (rotamasi)
• Isomerizzazione cis-trans Pro (10% dei
residui di Pro)
• Processo lento nel bilancio del folding
• Note anche come immunofilline
• Due famiglie:
• A) ciclofilline (legano l’immunosoppressore
ciclosporina A)
• B) FKBP12 (legano l’immunosoppressore
di
origine fungina FK506)
Distortions of -helices.
The majority of -helices in globular proteins are curved or distorted somewhat
compared with the standard Pauling-Corey model. These distortions arise from several
factors including:
1.The packing of buried helices against other secondary structure elements in the
core of the protein.
2.Proline residues induce distortions of around 20 degrees in the direction of the
helix axis. This is because proline cannot form a regular -helix due to steric
hindrance arising from its cyclic side chain which also blocks the main chain N
atom and chemically prevents it forming a hydrogen bond. Janet Thornton has
shown that proline causes two H-bonds in the helix to be broken since the NH
group of the following residue is also prevented from forming a good hydrogen
bond. Helices containing proline are usually long perhaps because shorter helices
would be destabilised by the presence of a proline residue too much. Proline occurs
more commonly in extended regions of polypeptide.
3.Solvent. Exposed helices are often bent away from the solvent region. This is
because the exposed C=O groups tend to point towards solvent to maximise their
H-bonding capacity, i.e. tend to form H-bonds to solvent as well as N-H groups.
This gives rise to a bend in the helix axis.
La cheratina è una proteina filamentosa ricca di zolfo, contenuto
nei residui amminoacidici di cisteina; è molto stabile e resistente. È
prodotta dai cheratinociti ed è il principale costituente dello strato
corneo dell'epidermide, delle unghie e di appendici quali capelli,
corna e piume.
I residui a e d (idrofobici) si
allineano sulla stesso lato
dell’elica
Il lato idrofobico di
un’elica si associa
con un’altra elica
CHERATINA
Passo dell’elica 5,1Å
3,5 residui per giro
Due eliche si avvolgono
l’una intorno all’altra in
senso sinistrorso:
Coiled coil
(avvolgimento avvolto)
Disulfide bridges
In addition to intra- and intermolecular hydrogen bonds, keratins
have large amounts of the sulfur-containing amino acid cysteine,
required for the disulfide bridges that confer additional strength and
rigidity by permanent, thermally-stable crosslinking. Human hair is
approximately 14% cysteine. The pungent smells of burning hair
and rubber are due to the sulfur compounds formed. Extensive
disulfide bonding contributes to the insolubility of keratins, except
in dissociating or reducing agents.
The more flexible and elastic keratins of hair have fewer interchain
disulfide bridges than the keratins in mammalian fingernails, ,
which are harder.
Diagramma di un desmosoma
Epidermolysis bullosa simplex (EBS) is a disorder resulting
from mutations in the genes encoding keratin 5 or keratin
14. Blister formation of EBS is within the basal keratinocyte
of the epidermis.
COLLAGENO Ripetizione della tripletta Gly-X-Y, dove X è spesso
Pro e Y è spesso Hyp (a volte Hyl)
Ogni catena forma un’elica sinistrorsa con tre
residui per giro e una distanza tra residui di 2,9 Å
Tripla elica allungata
Legami ad
idrogeno
Beta-sheet
Legami ad idrogeno
Catene
laterali
7Å
FIBROINA della seta
(-Gly-Ser-Gly-Ala-Gly-Ala)n
Foglietti beta antiparalleli le cui
catene si estendono parallelamente
all’asse della fibra.
FIBROINA della seta
(-Gly-Ser-Gly-Ala-Gly-Ala)n
Dalla struttura del foglietto beta
dipendono alcune delle proprietà
meccaniche della seta.
La seta , una delle fibre più
resistenti, non è praticamente
estensibile in quanto un suo
allungamento causerebbe la
rottura dei legami covalenti
della molecola che si trova in
una conformazione quasi
completamente estesa. La seta è
però flessibile perché i foglietti
beta vicini sono uniti da forze
deboli.
Reverse turns (ripiegamenti inversi)
A reverse turn is region of the polypeptide having a hydrogen bond from
one main chain carbonyl oxygen to the main chain N-H group 3 residues
along the chain (i.e. Oi to Ni+3). Helical regions are excluded from this
definition and turns between -strands form a special class of turn known
as the -hairpin.
-hairpins
-hairpins are one of the simplest super-secondary structures and are widespread in
globular proteins.
70% of -hairpins are less than 7 residues in length with the tworesidue turns forming the most noticeable component.
-a- motifs
Anti-parallel -strands can be linked by short lengths of polypeptide forming -hairpin
structures. In contrast, parallel -strands are connected by longer regions of chain which
cross the -sheet and frequently contain -helical segments. This motif is called the a- motif and is found in most proteins that have a parallel -sheet. The loop regions
linking the strands to the helical segments can vary greatly in length. The helix axis is
roughly parallel with the -strands and all three elements of secondary structure interact
forming a hydrophobic core. In certain proteins the loop linking the carboxy terminal
end of the first -strand to the amino terminal end of the helix is involved in binding of
ligands or substrates. The -a- motif almost always has a right-handed fold as
demonstrated in the figure.