Speaker: Alexey Amunts, Ph.D., Tenured group leader (Associate Professor), Departmentof Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden

Time: 15:00-16:30 p.m., July 31, 2023, GMT+8

Venue: LUI Che Woo Building (吕志和楼), Hall in the 3rd layer (三层大厅)

Abstract:

The mitoribosome translates specific mitochondrial mRNAs ana regulates energy production that is a signature of alleukaryotic life forms. We present cryo-EM analysesof 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. lt features a mitochondria-specific protein ms37 that links the assembly to translation initiation. A delivery of mRNA is then performed by a helical repeat factorLRPPRC 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.

Source: School of Life Science