16.2
Signalsequenzen und Sortierrezeptoren
Signalsequenzen sind kurze Aminosäuresequenzen, die neu synthetisierte Proteine an ihren richtigen Ort in der Zelle leiten. Klassische Signalsequenzen…
Sortiersignale sind Aminosäuresequenzen, die Proteine an ihren richtigen Platz in der Zelle leiten. Signalsequenzen variieren in der Länge, sind aber in der Regel 15 bis 20 Aminosäuren lang und flankieren die N-terminale Region einer Polypeptidkette.
Einige Proteine, wie z. B. Kernproteine, können entfernte Abschnitte von Aminosäureresten aufweisen, die während der Proteinfaltung zusammenkommen, um dreidimensionale Anordnungen zu bilden, die als Signalfelder bezeichnet werden.
Sortiersignale und Signalfelder werden in der Regel anhand der Aminosäureeigenschaften und nicht anhand der genauen Reihenfolge erkannt.
Proteine, die auf ein bestimmtes Zellorganell abzielen, weisen charakteristische Merkmale in ihren Signalsequenzen auf, wie z. B. Abschnitte hydrophober Reste, positiv geladene Aminosäuren, die sich mit hydrophoben Resten abwechseln, und durchsetzte Aminosäurereste mit Hydroxylgruppen.
Auf der Organelle vorhandene Signalrezeptoren identifizieren die entsprechenden Signalsequenzen und transportieren Proteine an den Zielort.
Sobald ein Protein sein Ziel erreicht hat, spalten Signalpeptidasen die Signalpeptide an ihrer C-terminalen Signalspaltstelle, während die Sortierrezeptoren recycelt werden, um nachfolgende Runden der Proteinsortierung zu katalysieren.
Durch die Modifikation der Sortiersignale können Proteine an einen anderen Ort geleitet werden. Zum Beispiel leitet das Hinzufügen der N-terminalen Signalsequenz von ER-Proteinen zu zytosolischen Proteinen diese in das endoplasmatische Retikulumlumen.
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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.