БИОХИМИЯ, 2020, том 85, вып. 12, с. 1788–1815

УДК 577.24

Экспансия «Натриевого мира» сквозь эволюционное время и таксономическое пространство

Обзор

© 2020 М.И. Козлова 1,2, И.М. Бушмакин 3, Ю.Д. Беляева 3, Д.Н. Шалаева 1, Д.В. Диброва 2, Д.А. Черепанов 4, А.Я. Мулкиджанян 1,2,3*

Оснабрюкский университет, физический факультет, 49069 Оснабрюк, Германия; электронная почта: amulkid@uos.de

НИИ физико-химической биологии имени А.Н. Белозерского, Московский государственный университет имени М.В. Ломоносова, 119991 Москва, Россия

Московский государственный университет имени М.В. Ломоносова, факультет биоинженерии и биоинформатики, 119991 Москва, Россия

Институт химической физики имени Н.Н. Семенова РАН, 119991 Москва, Россия

Поступила в редакцию 01.09.2020
После доработки 27.09.2020
Принята к публикации 27.09.2020

DOI: 10.31857/S0320972520120052

КЛЮЧЕВЫЕ СЛОВА: биоэнергетика, переносчик натрия, натрий-калиевый гомеостаз, ретиналь-связывающие белки, GPCR, агонист, сравнительная геномика, антибиотики, исследования лекарственных средств.

Аннотация

В 1986 г. Владимир Скулачев и его коллеги назвали «Натриевым миром» сообщество организмов, обладающих натрий (Na)-зависимой биоэнергетикой. Хотя к тому времени было обнаружено лишь несколько таких организмов, авторы проницательно отметили, что «большое таксономическое разнообразие организмов, использующих Na-цикл, указывает на повсеместное распространение этого нового типа мембрано-связанного преобразования энергии». Мы применили инструменты биоинформатики, чтобы проследить за расширением «Натриевого мира» в эволюционном времени и таксономическом пространстве. Так, в геномах прокариот были идентифицированы те семейства мембранных белков, которые коррелируют с использованием Na-потенциала для синтеза АТФ. Помимо известных переносчиков Na, было обнаружено множество не охарактеризованных семейств белков; большинство из них негомологичны изученным белкам. Кроме того, элементы натрий-зависимой энергетики были обнаружены у многих новых клад архей и бактерий, недавно идентифицированных методами метагеномики. Полученные данные свидетельствуют в пользу эволюционной первичности натрий-зависимой энергетики и ее преобладании в течение первых двух миллиардов лет истории Земли вплоть до насыщения атмосферы кислородом. Таким образом, полный потенциал натрий-зависимой энергетики для прокариот остается в значительной степени неоцененным. «Натриевый мир» расширялся за счет обретения новых функций Na-переносящими системами. В частности, большинство классов рецепторов, ассоциированных с G-белком (GPCR), являющихся мишенью почти половины всех известных лекарств, по-видимому, произошли от Na+-переносящих микробных родопсинов. При этом GPCR класса A с 700 представителями в геноме человека сохранили Na+-связывающий сайт между своими 7-ю трансмембранными спиралями вместе со способностью к транслокации Na+. Математическое моделирование показало, что GPCR класса A, по-видимому, используют энергию трансмембранного Na-потенциала для увеличения как своей чувствительности, так и селективности. Таким образом, GPCR, самое большое из представленных в геноме человека белковых семейств, происходит из «Натриевого мира», что говорит о необходимости изучения и других Na-зависимых ферментов эукариот.

Сноски

* Адресат для корреспонденции.

Финансирование

Работа выполнена при финансовой поддержке Немецкого научно-исследовательского общества (DFG), Немецкой службы академических обменов (DAAD), программы EvoCell Оснабрюкского университета, Программы развития МГУ им. М.В. Ломоносова (суперкомпьютеры «Чебышев» и «Ломоносов»), а также гранта Российского научного фонда (17-14-01314).

Благодарности

Мы выражаем особую благодарность Владимиру Скулачеву за его неизменный интерес к нашей работе; мы также благодарны докторам А.В. Богачеву, П. Диброву, М.Ю. Гальперину, Й. Кларе, Е.В. Кунину, К.С. Макаровой, Х.-Ю. Штайнхоффу, Н. Воскобойниковой и Ю.В. Вольфу за полезные дискуссии.

Конфликт интересов

Авторы заявляют об отсутствии конфликтов интересов.

Соблюдение этических норм

Данная работа не содержит исследований, в которых в качестве объектов были бы использованы люди или животные.

Дополнительные материалы

Приложение к статье на английском языке опубликовано на сайте журнала «Biochemistry» (Moscow) (http://protein.bio.msu.ru/biokhimiya/) и на сайте издательства Springer (https://link.springer.com/journal/10541), том 85, вып. 12, 2020.

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