Cryo-EM structure of a 40 kDa SAM-IV riboswitch RNA at 3.7 Å resolution

Zhang, Kaiming; Li, Shanshan; Kappel, Kalli; Pintilie, Grigore; Su, Zhaoming; Mou, Tung-Chung; Schmid, Michael F.; Das, Rhiju; Chiu, Wah

doi:10.1038/s41467-019-13494-7

Title: Cryo-EM structure of a 40 kDa SAM-IV riboswitch RNA at 3.7 Å resolution

Journal Article · 03 December 2019 · Nature Communications

DOI: https://doi.org/10.1038/s41467-019-13494-7 · OSTI ID:1594993

^[1];

^[1]; Pintilie, Grigore ^[1];

^[1]; Mou, Tung-Chung ^[2];

^[3];

^[1]; Chiu, Wah ^[3]

Stanford Univ., CA (United States)
Univ. of Montana, Missoula, MT (United States)
SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL); Stanford Univ., CA (United States)

Specimens below 50 kDa have generally been considered too small to be analyzed by single-particle cryo-electron microscopy (cryo-EM). The high flexibility of pure RNAs makes it difficult to obtain high-resolution structures by cryo-EM. In bacteria, riboswitches regulate sulfur metabolism through binding to the S-adenosylmethionine (SAM) ligand and offer compelling targets for new antibiotics. SAM-I, SAM-I/IV, and SAM-IV are the three most commonly found SAM riboswitches, but the structure of SAM-IV is still unknown. Here, we report the structures of apo and SAM-bound SAM-IV riboswitches (119-nt, ~40 kDa) to 3.7 Å and 4.1 Å resolution, respectively, using cryo-EM. The structures illustrate homologies in the ligand-binding core but distinct peripheral tertiary contacts in SAM-IV compared to SAM-I and SAM-I/IV. Our results demonstrate the feasibility of resolving small RNAs with enough detail to enable detection of their ligand-binding pockets and suggest that cryo-EM could play a role in structure-assisted drug design for RNA.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: National Science Foundation (NSF); National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-76SF00515; P41GM103832; R01GM079429; U54GM103297; P20GM103546; GM112579; R21AI145647

OSTI ID:: 1594993

Journal Information:: Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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