16.2
Sequenze di segnali e recettori di ordinamento
Le sequenze segnale sono brevi sequenze di amminoacidi che guidano le proteine appena sintetizzate nella loro corretta posizione all'interno della cel…
I segnali di smistamento sono sequenze di amminoacidi che guidano le proteine verso la loro corretta posizione all'interno della cellula. Le sequenze segnale variano in lunghezza, ma di solito sono lunghe da 15 a 20 amminoacidi, fiancheggiando la regione N-terminale di una catena polipeptidica.
Alcune proteine, come le proteine nucleari, possono avere tratti distanti di residui di amminoacidi che si uniscono durante il ripiegamento delle proteine per formare disposizioni tridimensionali chiamate patch segnale.
I segnali di smistamento e le patch di segnale sono solitamente riconosciuti in base alle proprietà degli amminoacidi piuttosto che alla sequenza esatta.
Le proteine mirate a un particolare organello cellulare hanno caratteristiche nelle loro sequenze segnale, come tratti di residui idrofobici, amminoacidi caricati positivamente alternati a residui idrofobici e residui di amminoacidi intervallati con gruppi ossidrilici.
I recettori di segnale presenti sull'organello identificano le sequenze di segnale corrispondenti e trasportano le proteine nella posizione bersaglio.
Una volta che una proteina raggiunge la sua destinazione, le peptidasi segnale scindono i peptidi segnale nel loro sito di scissione del segnale C-terminale, mentre i recettori di smistamento vengono riciclati per catalizzare i successivi cicli di smistamento delle proteine.
La modifica dei segnali di smistamento può indirizzare le proteine in una posizione diversa. Ad esempio, l'aggiunta della sequenza del segnale N-terminale delle proteine ER alle proteine citosoliche le indirizza al lume del reticolo endoplasmatico.
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Q1: What are signal sequences and how long are they typically?
Signal sequences are amino acid sequences that guide proteins to their proper location inside the cell. They are usually 15 to 20 amino acids long and flank the N-terminal region of a polypeptide chain. Classical signal sequences can range from 15 to 60 amino acids and contain a conserved segment of basic residues, a hydrophobic core, and a C-terminus rich in polar residues.
Q2: How do sorting receptors recognize and transport proteins to their destinations?
Sorting receptors present on organelles identify corresponding signal sequences based on amino acid properties rather than exact sequence. These receptors can be soluble, like nuclear receptors, or membrane-bound, as found in mitochondria and chloroplasts. After delivering proteins to their target location, sorting receptors are recycled for multiple rounds of protein sorting.
Q3: What happens to signal sequences after proteins reach their destination?
Signal peptidases cleave signal peptides at their C-terminal signal cleavage site once proteins reach their destination. However, some signal sequences remain permanently associated with proteins without being cleaved, particularly in nuclear proteins and transmembrane proteins. The signal cleavage site features a -3-1 sequence motif containing amino acids with short side chains.
Q4: What are signal patches and how do they differ from classical signal sequences?
Signal patches are three-dimensional arrangements formed by distant stretches of amino acid residues that come together during protein folding, particularly in nuclear proteins. Unlike classical N-terminal signal sequences, signal patches are internal and recognized based on their spatial structure rather than linear sequence. They guide proteins to their proper organellar location through their distinctive three-dimensional properties.
Q5: What characteristic features do signal sequences contain for organellar targeting?
Signal sequences contain characteristic features such as stretches of hydrophobic residues, positively charged amino acids alternating with hydrophobic residues, and interspersed amino acid residues with hydroxyl-groups. These properties allow sorting receptors to recognize and bind specific signal sequences. Signal-anchor sequences, which are rich in hydrophobic amino acids, help anchor transmembrane proteins within organellar membranes.
Q6: How can modifying signal sequences change where proteins are targeted?
Modifying or adding signal sequences can redirect proteins to different cellular locations. For example, adding the N-terminal signal sequence of endoplasmic reticulum proteins to cytosolic proteins routes them to the ER lumen instead of their original destination. This demonstrates that signal sequences are the primary determinants of protein localization.
Q7: What diseases are associated with defective signal sequences?
Mutations or removal of signal sequences leads to defective protein routing and is associated with inherited kidney diseases, autoimmune diseases, cardiovascular diseases, and several metabolic disorders. Proper signal sequence recognition and protein sorting are essential for maintaining cellular function and preventing pathological conditions.