Location of the Actual Signal in the Negatively Charged Leader Sequence Involved in the Import into the Mitochondrial Matrix Space
Year: 2003
Type: article
Abstract: Proteins destined for the mitochondrial matrix space have leader sequences that are typically present at the most N-terminal end of the nuclear-encoded precursor protein. The leaders are rich in positive charges and usually deficient of negative charges. This observation led to the acid-chain hypothesis to explain how the leader sequences interact with negatively charged receptor proteins. Here we show using both chimeric leaders and one from isopropyl malate synthase that possesses a negative charge that the leader need not be at the very N terminus of the precursor. Experiments were performed with modified non-functioning leader sequences fused to either the native or a non-functioning leader of aldehyde dehydrogenase so that an internal leader sequence could exist. The internal leader is sufficient for the import of the modified precursor protein. It appears that this leader still needs to form an amphipathic helix just like the normal N-terminal leaders do. This internal leader could function even if the most N-terminal portion contained negative charges in the first 7-11 residues. If the first 11 residues were deleted from isopropyl malate synthase, the resulting protein was imported more successfully than the native protein. It appears that precursors that carry negatively charged leaders use an internal signal sequence to compensate for the non-functional segment at the most N-terminal portion of the protein.
Source: Journal of Biological Chemistry
Institution: Purdue University West Lafayette
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1992744933