A Caltech Library Service

A chemically synthesized pre-sequence of an imported mitochondrial protein can form an amphiphilic helix and perturb natural and artificial phospholipid bilayers

Roise, David and Horvath, Suzanna J. and Tomich, John M. and Richards, John H. and Schatz, Gottfried (1986) A chemically synthesized pre-sequence of an imported mitochondrial protein can form an amphiphilic helix and perturb natural and artificial phospholipid bilayers. EMBO Journal, 5 (6). pp. 1327-1334. ISSN 0261-4189. PMCID PMC1166944.

[img] PDF - Published Version
See Usage Policy.


Use this Persistent URL to link to this item:


Subunit IV of yeast cytochrome oxidase is made in the cytoplasm with a transient pre-sequence of 25 amino acids which is removed upon import of the protein into mitochondria. To study the function of this cleavable pre-sequence in mitochondrial protein import, three peptides representing 15, 25 or 33 amino-terminal residues of the subunit IV precursor were chemically synthesized. All three peptides were freely soluble in aqueous buffers, yet inserted spontaneously from an aqueous subphase into phospholipid monolayers up to an extrapolated limiting monolayer pressure of 40-50 mN/m. The two longer peptides also caused disruption of unilamellar liposomes. This effect was increased by a diffusion potential, negative inside the liposomes, and decreased by a diffusion potential of opposite polarity. The peptides, particularly the two longer ones, also uncoupled respiratory control of isolated yeast mitochondria. The 25-residue peptide had little secondary structure in aqueous buffer but became partly alpha-helical in the presence of detergent micelles. Based on the amino acid sequence of the peptides, a helical structure would have a highly asymmetric distribution of charged and apolar residues and would be surface active. Amphiphilic helicity appears to be a general feature of mitochondrial pre-sequences. We suggest that this feature plays a crucial role in transporting proteins into mitochondria.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Additional Information:© 1986 IRL Press Limited. Received on 12 March 1986; revised on 4 April 1986. We wish to thank Dr K.Verner for the electron micrographs and Dr J.-Y.Chang of Ciba-Geigy, Basel for the amino acid analyses. We also thank Drs D.Allison, M. Dihanich, E.Hurt, L.Tamm, A.van Loon, and K.Verner, and C.Bibus, M. Eilers, and C.Witte for critically reading the manuscript, and J.Seelig, P.MacDonald, S.Stankowski, and H.Vogel for their help and for stimulating discussions. Dr L.Tamm was also especially helpful with the monolayer experiments. Finally, we would like to acknowledge gratefully the use of the Microchemical Facility in the laboratory of Professor Leroy E.Hood at Caltech. This study was supported by grants 3.394-0.83 and 3.660-0.84 from the Swiss National Science Foundation and a postdoctoral fellowship (to D.R.) from the Jane Coffin Childs Memorial Fund for Medical Research.
Funding AgencyGrant Number
Swiss National Science Foundation3.394-0.83
Swiss National Science Foundation3.660-0.84
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
Subject Keywords:amphiphilic helix; membrane perturbation; mitochondria; pre-sequence; protein import
Issue or Number:6
PubMed Central ID:PMC1166944
Record Number:CaltechAUTHORS:20150428-161442866
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:57072
Deposited On:30 Apr 2015 20:43
Last Modified:03 Oct 2019 08:20

Repository Staff Only: item control page