A minimal motif for sequence recognition by mitochondrial transcription factor A (TFAM)

Choi, Woo Suk; Garcia-Diaz, Miguel

doi:10.1093/nar/gkab1230

A minimal motif for sequence recognition by mitochondrial transcription factor A (TFAM)

Journal Article · Mon Dec 20 00:00:00 EST 2021 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkab1230· OSTI ID:1836600

^[1]; Garcia-Diaz, Miguel ^[1]

Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA

Abstract

Mitochondrial transcription factor A (TFAM) plays a critical role in mitochondrial transcription initiation and mitochondrial DNA (mtDNA) packaging. Both functions require DNA binding, but in one case TFAM must recognize a specific promoter sequence, while packaging requires coating of mtDNA by association with non sequence-specific regions. The mechanisms by which TFAM achieves both sequence-specific and non sequence-specific recognition have not yet been determined. Existing crystal structures of TFAM bound to DNA allowed us to identify two guanine-specific interactions that are established between TFAM and the bound DNA. These interactions are observed when TFAM is bound to both specific promoter sequences and non-sequence specific DNA. These interactions are established with two guanine bases separated by 10 random nucleotides (GN10G). Our biochemical results demonstrate that the GN10G consensus is essential for transcriptional initiation and contributes to facilitating TFAM binding to DNA substrates. Furthermore, we report a crystal structure of TFAM in complex with a non sequence-specific sequence containing a GN10G consensus. The structure reveals a unique arrangement in which TFAM bridges two DNA substrates while maintaining the GN10G interactions. We propose that the GN10G consensus is key to facilitate the interaction of TFAM with DNA.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)

Sponsoring Organization:: National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-98CH10886; SC0012704

OSTI ID:: 1836600

Alternate ID(s):: OSTI ID: 1982712

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 1 Vol. 50; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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