Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities

Cytochrome <i>c</i> is one of the most prominent representatives of peripheral membrane proteins. Besides functioning as an electron transfer carrier in the mitochondrial respiratory chain, it can acquire peroxidase capability, promote the self-assembly of α-synuclein, and function as a...

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Main Author: Reinhard Schweitzer-Stenner
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/2/198
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author Reinhard Schweitzer-Stenner
author_facet Reinhard Schweitzer-Stenner
author_sort Reinhard Schweitzer-Stenner
collection DOAJ
description Cytochrome <i>c</i> is one of the most prominent representatives of peripheral membrane proteins. Besides functioning as an electron transfer carrier in the mitochondrial respiratory chain, it can acquire peroxidase capability, promote the self-assembly of α-synuclein, and function as a scavenger of superoxide. An understanding of its function requires knowledge of how the protein interacts with the inner membrane of mitochondria. The first part of this article provides an overview of a variety of experiments that were aimed at exploring the details of cytochrome <i>c</i> binding to anionic lipid liposomes, which serve as a model system for the inner membrane. While cytochrome <i>c</i> binding involves a conformational change from a folded into a partially disordered state, α-synuclein is intrinsically disordered in solution and subjected to a partial coil -> helix transition on membranes. Depending on the solution conditions and the surface density of α-synuclein, the protein facilitates the self-assembly into oligomers and fibrils. As for cytochrome <i>c</i>, results of binding experiments are discussed. In addition, the article analyzes experiments that explored α-synuclein aggregation. Similarities and differences between cytochrome <i>c</i> and α-synuclein binding are highlighted. Finally, the article presents a brief account of the interplay between cytochrome <i>c</i> and α-synuclein and its biological relevance.
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spelling doaj-art-1ba8d51a431744e6ac41e373a197fb6c2025-08-20T02:44:59ZengMDPI AGBiomolecules2218-273X2025-01-0115219810.3390/biom15020198Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and DissimilaritiesReinhard Schweitzer-Stenner0Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USACytochrome <i>c</i> is one of the most prominent representatives of peripheral membrane proteins. Besides functioning as an electron transfer carrier in the mitochondrial respiratory chain, it can acquire peroxidase capability, promote the self-assembly of α-synuclein, and function as a scavenger of superoxide. An understanding of its function requires knowledge of how the protein interacts with the inner membrane of mitochondria. The first part of this article provides an overview of a variety of experiments that were aimed at exploring the details of cytochrome <i>c</i> binding to anionic lipid liposomes, which serve as a model system for the inner membrane. While cytochrome <i>c</i> binding involves a conformational change from a folded into a partially disordered state, α-synuclein is intrinsically disordered in solution and subjected to a partial coil -> helix transition on membranes. Depending on the solution conditions and the surface density of α-synuclein, the protein facilitates the self-assembly into oligomers and fibrils. As for cytochrome <i>c</i>, results of binding experiments are discussed. In addition, the article analyzes experiments that explored α-synuclein aggregation. Similarities and differences between cytochrome <i>c</i> and α-synuclein binding are highlighted. Finally, the article presents a brief account of the interplay between cytochrome <i>c</i> and α-synuclein and its biological relevance.https://www.mdpi.com/2218-273X/15/2/198cytochrome <i>c</i>α-synucleinperipheral membrane proteinselectrostatic and hydrophobic bindingmolecular crowdingα-synuclein self-assembly
spellingShingle Reinhard Schweitzer-Stenner
Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities
Biomolecules
cytochrome <i>c</i>
α-synuclein
peripheral membrane proteins
electrostatic and hydrophobic binding
molecular crowding
α-synuclein self-assembly
title Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities
title_full Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities
title_fullStr Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities
title_full_unstemmed Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities
title_short Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities
title_sort order to disorder and disorder to order transitions of proteins upon binding to phospholipid membranes common ground and dissimilarities
topic cytochrome <i>c</i>
α-synuclein
peripheral membrane proteins
electrostatic and hydrophobic binding
molecular crowding
α-synuclein self-assembly
url https://www.mdpi.com/2218-273X/15/2/198
work_keys_str_mv AT reinhardschweitzerstenner ordertodisorderanddisordertoordertransitionsofproteinsuponbindingtophospholipidmembranescommongroundanddissimilarities