Work

A Regional Net Charge and Structural Compensation Model to Explain How Negatively Charged Amino Acids Can Be Accepted within a Mitochondrial Leader Sequence

Year: 1998

Type: article

Abstract: Mitochondrial leader sequences have been found to be statistically enriched for positively charged residues, with only a few known leader sequences possessing negatively charged residues. Mutational studies that have introduced negatively charged residues into various leader sequences have shown a general, but not absolute, trend toward reduced import. The leader sequence of rat liver aldehyde dehydrogenase has been previously determined by NMR to form a helix-linker-helix structure. A negative charge introduced into this leader did not prevent import, provided that a net positive charge remained in the N-helical segment. When the net charge of the N-terminal helical segment was reduced to zero, import could be recovered by removing the linker, which resulted in a longer, more stable leader. This structural recovery of import was effective enough to compensate for a net charge of zero within the first 10 residues, even when a glutamate is the first charged side chain presented in the sequence.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.273.45.29389

Authors: Thomas S. Heard, Henry Weiner

Institution: Purdue University West Lafayette

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funders: Purdue University, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute of General Medical Sciences