5lm7
Crystal structure of the lambda N-Nus factor complex
Structural highlights
FunctionNUSA_ECOLI Participates in both transcription termination and antitermination. Involved in a variety of cellular and viral termination and antitermination processes, such as Rho-dependent transcriptional termination, intrinsic termination, and phage lambda N-mediated transcriptional antitermination. Also important for coordinating the cellular responses to DNA damage by coupling the processes of nucleotide excision repair and translesion synthesis to transcription.[1] [2] [3] [4] [5] [6] [7] [8] [9] Publication Abstract from PubMedlambdaN-mediated processive antitermination constitutes a paradigmatic transcription regulatory event, during which phage protein lambdaN, host factors NusA, NusB, NusE and NusG, and an RNA nut site render elongating RNA polymerase termination-resistant. The structural basis of the process has so far remained elusive. Here we describe a crystal structure of a lambdaN-NusA-NusB-NusE-nut site complex and an electron cryo-microscopic structure of a complete transcription antitermination complex, comprising RNA polymerase, DNA, nut site RNA, all Nus factors and lambdaN, validated by crosslinking/mass spectrometry. Due to intrinsic disorder, lambdaN can act as a multiprotein/RNA interaction hub, which, together with nut site RNA, arranges NusA, NusB and NusE into a triangular complex. This complex docks via the NusA N-terminal domain and the lambdaN C-terminus next to the RNA exit channel on RNA polymerase. Based on the structures, comparative crosslinking analyses and structure-guided mutagenesis, we hypothesize that lambdaN mounts a multipronged strategy to reprogram the transcriptional machinery, which may include (1) the lambdaN C terminus clamping the RNA exit channel, thus stabilizing the DNA:RNA hybrid; (2) repositioning of NusA and RNAP elements, thus redirecting nascent RNA and sequestering the upstream branch of a terminator hairpin; and (3) hindering RNA engagement of termination factor rho and/or obstructing rho translocation on the transcript. Structural basis for lambdaN-dependent processive transcription antitermination.,Said N, Krupp F, Anedchenko E, Santos KF, Dybkov O, Huang YH, Lee CT, Loll B, Behrmann E, Burger J, Mielke T, Loerke J, Urlaub H, Spahn CMT, Weber G, Wahl MC Nat Microbiol. 2017 Apr 28;2:17062. doi: 10.1038/nmicrobiol.2017.62. PMID:28452979[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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