Document Detail


Interaction of the Tim44 C-terminal domain with negatively charged phospholipids.
MedLine Citation:
PMID:  19863062     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The translocation of proteins from the cytosol into the mitochondrial matrix is mediated by the coordinated action of the TOM complex in the outer membrane, as well as the TIM23 complex and its associated protein import motor in the inner membrane. The focus of this work is the peripheral inner membrane protein Tim44. Tim44 is a vital component of the mitochondrial protein translocation motor that anchors components of the motor to the TIM23 complex. For this purpose, Tim44 associates with the import channel by direct interaction with the Tim23 protein. Additionally, it was shown in vitro that Tim44 associates with acidic model membranes, in particular those containing cardiolipin. The latter interaction was shown to be mediated by the carboxy-terminal domain of Tim44 [Weiss, C., et al. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 8890-8894]. The aim of this study was to determine the precise recognition site for negative lipids in the C-terminal domain of Tim44. In particular, we wanted to examine the recently suggested hypothesis that acidic phospholipids associate with Tim44 via a hydrophobic cavity that is observed in the high-resolution structure of the C-terminal domain of the protein [Josyula, R., et al. (2006) J. Mol. Biol. 359, 798-804]. Molecular dynamics simulations suggest that (i) the hydrophobic tail of lipids may interact with Tim44 via the latter's hydrophobic cavity and (ii) a region, located in the N-terminal alpha-helix of the C-terminal domain (helices A1 and A2), may serve as a membrane attachment site. To validate this assumption, N-terminal truncations of yeast Tim44 were examined for their ability to bind cardiolipin-containing phospholipid vesicles. The results indicate that removal of the N-terminal alpha-helix (helix A1) abolishes the capacity of Tim44 to associate with cardiolipin-containing liposomes. We suggest that helices A1 and A2, in Tim44, jointly promote the association of the protein with acidic phospholipids.
Authors:
Milit Marom; Roman Safonov; Shay Amram; Yoav Avneon; Esther Nachliel; Menachem Gutman; Keren Zohary; Abdussalam Azem; Yossi Tsfadia
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  48     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2009-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11185-95     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cardiolipins / chemistry,  metabolism
Carrier Proteins / chemistry*,  metabolism*
Hydrophobicity
Liposomes / chemistry,  metabolism
Membrane Proteins
Mitochondrial Membrane Transport Proteins / chemistry,  metabolism
Mitochondrial Proteins
Phospholipids / chemistry,  metabolism*
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Protein Transport / physiology*
Static Electricity
Chemical
Reg. No./Substance:
0/Cardiolipins; 0/Carrier Proteins; 0/Liposomes; 0/Membrane Proteins; 0/Mitochondrial Membrane Transport Proteins; 0/Mitochondrial Proteins; 0/Phospholipids; 0/TIMM44 protein, human; 0/TOM translocase

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