{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:23:12Z","timestamp":1785417792282,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,27]]},"group-title":"Biochemistry","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R35 GM138157"],"award-info":[{"award-number":["R35 GM138157"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R24GM154185"],"award-info":[{"award-number":["R24GM154185"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2033441"],"award-info":[{"award-number":["2033441"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1846908"],"award-info":[{"award-number":["1846908"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  SufR is an iron\u2013sulfur ([4Fe-4S]) cluster-containing transcription factor belonging to an uncharacterized domain family (COG2345). It has been shown to negatively regulate the sulfur utilization factor (SUF) Fe-S biogenesis system in several Gram-negative and Gram-positive bacteria including Cyanobacteria, Mycobacteria and Streptomyces. The structural basis for its DNA recognition and transcriptional regulation by the SufR-like proteins remains enigmatic. In this study, we present the cryo-EM structure of\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  SufR bound to its promoter, revealing a new domain architecture. Our structural, biochemical and molecular analyses show that SufR possesses an unusual [4Fe-4S] cluster coordination environment in the sensory domain and recognizes its promoter via a dual-module mechanism using both the AT-hook and the helix-turn-helix (HTH) DNA-binding motif in the DNA-binding domain. This DNA recognition strategy differs from a canonical winged HTH transcription factor. Moreover, our bioinformatic analysis and structural modeling suggest that SufR and SufR-like proteins in the COG2345 family represent a large, previously uncharacterized family of transcription factors widely distributed across bacteria and archaea. Together, these findings establish SufR-like proteins as a new model for transcriptional regulation by Fe-S transcription factors in prokaryotes and uncover the underappreciated evolutionary versatility of AT-hooks.\n                <\/jats:p>","DOI":"10.64898\/2025.12.26.696629","type":"posted-content","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T22:40:10Z","timestamp":1766875210000},"source":"Crossref","is-referenced-by-count":0,"title":["A New Paradigm of Transcriptional Regulation by the SufR-Like Iron-Sulfur Transcription Factors"],"prefix":"10.64898","author":[{"given":"Zhifang","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA"},{"name":"Biortus Biosciences Co., Ltd, Jiangyin, Jiangsu, 214437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Davulcu","sequence":"additional","affiliation":[{"name":"Pacific Northwest Center for Cryo-EM, Oregon Health & Science University, Portland, Oregon, USA"},{"name":"Pacific Northwest National Laboratory, Environmental Molecular Sciences Laboratory, Richland, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"de 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