Shaping a signal: studies on non-contiguous residues in an intracellular serpin that constitute a novel nuclear protein import signal

Eukaryotic cells contain membrane-bound organelles like the nucleus, endoplasmic reticulum and mitochondria, and use specific mechanisms to direct proteins from their site of synthesis to their target organelle. In nuclear proteins, sequence motifs termed nuclear localization signals (NLSs) direct engagement with the nuclear pore complex and translocation from cytoplasm to nucleus. All NLSs described so far consist of 5-7 contiguous basic residues. We propose to study a novel NLS that we recently discovered on an intracellular serpin. This comprises non-contiguous residues that together form a basic patch on the mature protein, and is the first example of a conformational NLS.