title: Helix-helix interactions in membrane domains of bitopic proteins: Specificity and role of lipid environment.
abstract: Interaction between transmembrane helices often determines biological activity of membrane proteins. Bitopic proteins, a broad subclass of membrane proteins, form dimers containing two membrane-spanning helices. Some aspects of their structure-function relationship cannot be fully understood without considering the protein-lipid interaction, which can determine the protein conformational ensemble. Experimental and computer modeling data concerning transmembrane parts of bitopic proteins are reviewed in the present paper. They highlight the importance of lipid-protein interactions and resolve certain paradoxes in the behavior of such proteins. Besides, some properties of membrane organization provided a clue to understanding of allosteric interactions between distant parts of proteins. Interactions of these kinds appear to underlie a signaling mechanism, which could be widely employed in the functioning of many membrane proteins. Treatment of membrane proteins as parts of integrated fine-tuned proteolipid system promises new insights into biological function mechanisms and approaches to drug design. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation; National Research Centre "Kurchatov Institute", Akad. Kurchatova pl. 1, Moscow, 123182, Russian Federation. Electronic address: bon@nmr.ru.
authors.forename: Eduard V
authors.initials: EV
authors.lastname: Bocharov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation.
authors.forename: Konstantin S
authors.initials: KS
authors.lastname: Mineev
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninskiy prospect 31/5, Moscow, 119071, Russian Federation.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Pavlov
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninskiy prospect 31/5, Moscow, 119071, Russian Federation; National University of Science and Technology "MISiS", Leninskiy prospect 4, Moscow, 119049, Russian Federation.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Akimov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Kuznetsov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation; Higher School of Economics, Myasnitskaya ul. 20, Moscow, 101000, Russian Federation.
authors.forename: Roman G
authors.initials: RG
authors.lastname: Efremov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation. Electronic address: aars@nmr.ru.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D000072756:Protein Conformation, alpha-Helical; D017510:Protein Folding; D055503:Protein Multimerization; D015398:Signal Transduction; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D008565:Membrane Proteins
keywords: bitopic membrane protein; lipid density fluctuations; protein-lipid and protein-protein interactions; receptor tyrosine kinase; signal transduction; transmembrane domain