题 目：How genes become machines in mitochondria

主 讲：Alexey Amunts 教授

时 间：2023年8月2日下午16:00-17:30

地 点：琳恩图书馆111报告厅

报告摘要：

The mitoribosome translates specific mitochondrial mRNAs and regulates energy production that is a signature of all eukaryotic life forms. We present cryo-EM analyses of its assembly intermediates, mRNA binding process, and nascent polypeptide delivery to the membrane. To study the assembly mechanism, we determined a series of the small mitoribosomal subunit intermediates in complex with auxiliary factors that explain how action of step-specific factors establishes the catalytic mitoribosome. It features a mitochondria-specific protein ms37 that links the assembly to translation initiation. A delivery of mRNA is then performed by a helical repeat factor LRPPRC that forms a stable complex with a small binding partner SLIRP. In mammals, LRPPRC stabilises mRNAs co-transcriptionally, thus it links the entire gene expression system. Through the translation cycle, a nascent polypeptide is delivered to the mitochondrial inner membrane, and we report the mitoribosome structure bound to the insertase OXA1, which elucidates the basis for protein synthesis coupling to membrane delivery. Finally, comparative structural and biochemical analyses reveal functionally important binding of cofactors iron-sulfur clusters, polyamines, NAD, ATP and GDP. Together with experimental identification of specific rRNA and protein modifications, the data illuminate principal components responsible for the translation of genetic material in mitochondria.

嘉宾简介：

Alexey Amunts is Associate Professor at Science for Life Laboratory, Stockholm. For his PhD, he studied structural biology at the Tel Aviv University and specialized in bioenergetics. Following his postdoctoral studies at the MRC Laboratory of Molecular Biology with Venki Ramakrishnan on cryo-EM of a mitoribosome that became known as the ‘Resolution Revolution’, he established an independent group in Stockholm in 2016. The group is funded by the European Research Council and studies mitochondrial protein synthesis and energy production at the molecular and cellular level. Alexey Amunts is EMBO Young Investigator, and the recipient of the Cancer Foundation Junior Investigator Award.