6sh6

From Proteopedia

Crystal structure of the human DEAH-helicase DHX15 in complex with the NKRF G-patch bound to ADP

PDB ID 6sh6

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Structural highlights

6sh6 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.85Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DHX15_HUMAN Pre-mRNA processing factor involved in disassembly of spliceosomes after the release of mature mRNA. In cooperation with TFIP11 seem to be involved in the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns.^[1]

Publication Abstract from PubMed

RNA helicases of the DEAH/RHA family are involved in many essential cellular processes, such as splicing or ribosome biogenesis, where they remodel large RNA-protein complexes to facilitate transitions to the next intermediate. DEAH helicases couple adenosine triphosphate (ATP) hydrolysis to conformational changes of their catalytic core. This movement results in translocation along RNA, which is held in place by auxiliary C-terminal domains. The activity of DEAH proteins is strongly enhanced by the large and diverse class of G-patch activators. Despite their central roles in RNA metabolism, insight into the molecular basis of G-patch-mediated helicase activation is missing. Here, we have solved the structure of human helicase DHX15/Prp43, which has a dual role in splicing and ribosome assembly, in complex with the G-patch motif of the ribosome biogenesis factor NKRF. The G-patch motif binds in an extended conformation across the helicase surface. It tethers the catalytic core to the flexibly attached C-terminal domains, thereby fixing a conformation that is compatible with RNA binding. Structures in the presence or absence of adenosine diphosphate (ADP) suggest that motions of the catalytic core, which are required for ATP binding, are still permitted. Concomitantly, RNA affinity, helicase, and ATPase activity of DHX15 are increased when G-patch is bound. Mutations that detach one end of the tether but maintain overall binding severely impair this enhancement. Collectively, our data suggest that the G-patch motif acts like a flexible brace between dynamic portions of DHX15 that restricts excessive domain motions but maintains sufficient flexibility for catalysis.

Structural basis for DEAH-helicase activation by G-patch proteins.,Studer MK, Ivanovic L, Weber ME, Marti S, Jonas S Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7159-7170. doi:, 10.1073/pnas.1913880117. Epub 2020 Mar 16. PMID:32179686^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yoshimoto R, Kataoka N, Okawa K, Ohno M. Isolation and characterization of post-splicing lariat-intron complexes. Nucleic Acids Res. 2009 Feb;37(3):891-902. doi: 10.1093/nar/gkn1002. Epub 2008, Dec 22. PMID:19103666 doi:http://dx.doi.org/10.1093/nar/gkn1002
↑ Studer MK, Ivanović L, Weber ME, Marti S, Jonas S. Structural basis for DEAH-helicase activation by G-patch proteins. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7159-7170. PMID:32179686 doi:10.1073/pnas.1913880117