9dci
Mycobacterium tuberculosis UvrD1 dimer: apo compact conformation.
Structural highlights
FunctionUVRD1_MYCTU DNA-dependent ATPase, acting on dsDNA with a 3'-ssDNA tail, unwinding with 3'-to 5'-polarity. A minimal tail of 18 nt is required for activity. Also highly efficient on nicked DNA. Involved in the post-incision events of nucleotide excision repair, as well as in nitrosative and oxidative stress response and possibly in persistence in the host. Inhibits RecA-mediated DNA strand exchange; this does not require ATPase activity. When combined with UvrA greatly inhibits RecA-mediated DNA strand exchange.[1] [2] [3] Publication Abstract from PubMedUvrD-family helicases are superfamily 1A motor proteins that function during DNA replication, recombination, repair, and transcription. UvrD family monomers translocate along single-stranded (ss) DNA but need to be activated by dimerization to unwind DNA in the absence of force or accessory factors. However, prior structural studies have only revealed monomeric complexes. Here, we report the first structures of a dimeric UvrD-family helicase, Mycobacterium tuberculosis UvrD1, both free and bound to a DNA junction. In each structure, the dimer interface occurs between the 2B subdomains of each subunit. The apo UvrD1 dimer is observed in symmetric compact and extended forms indicating substantial flexibility. This symmetry is broken in the DNA-bound dimer complex with leading and trailing subunits adopting distinct conformations. Biochemical experiments reveal that the Escherichia coli UvrD dimer shares the same 2B-2B interface. In contrast to the dimeric structures, an inactive, autoinhibited UvrD1 DNA-bound monomer structure reveals 2B subdomain-DNA contacts that are likely inhibitory. The major reorientation of the 2B subdomains that occurs upon UvrD1 dimerization prevents these duplex DNA interactions, thus relieving the autoinhibition. These structures reveal that the 2B subdomain serves a major regulatory role rather than participating directly in DNA unwinding. Structural basis for dimerization and activation of UvrD-family helicases.,Chadda A, Nguyen B, Lohman TM, Galburt EA Proc Natl Acad Sci U S A. 2025 Mar 11;122(10):e2422330122. doi: , 10.1073/pnas.2422330122. Epub 2025 Mar 6. PMID:40048277[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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