6ERQ

Structure of the human mitochondrial transcription initiation complex at the HSP promoter

Summary for 6ERQ

• Entry DOI: 10.2210/pdb6erq/pdb
• Descriptor: Transcription factor A, mitochondrial, Non-Template DNA, Template DNA, ... (5 entities in total)
• Functional Keywords: mitochondria, transcription, initiation, polymerase
• Biological source: Homo sapiens (Human); More
• Cellular location: Mitochondrion: Q00059 O00411 Q9H5Q4
• Total number of polymer chains: 10
• Total formula weight: 453220.41

Authors

Hillen, H.S.,Morozov, Y.I.,Sarfallah, A.,Temiakov, D.,Cramer, P. (deposition date: 2017-10-18, release date: 2017-11-15, Last modification date: 2024-05-01)

Primary citation

Hillen, H.S.,Morozov, Y.I.,Sarfallah, A.,Temiakov, D.,Cramer, P.
Structural Basis of Mitochondrial Transcription Initiation.
Cell, 171:1072-1081.e10, 2017

PubMed Abstract: Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria.

PubMed: 29149603
DOI: 10.1016/j.cell.2017.10.036

Experimental method

X-RAY DIFFRACTION (4.5 Å)