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7xhf

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Crystal structure of the NTF2L domain of human G3BP1 in complex with the USP10 derived peptide

Structural highlights

7xhf is a 4 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 2.68Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

G3BP1_HUMAN May be a regulated effector of stress granule assembly. Phosphorylation-dependent sequence-specific endoribonuclease in vitro. Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR. ATP- and magnesium-dependent helicase. Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends. Unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency. Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA.^[1] ^[2]

Publication Abstract from PubMed

Stress granules (SGs) are cytoplasmic biomolecular condensates containing proteins and RNAs in response to stress. Ras-GTPase-activating protein binding protein 1 (G3BP1) is a core SG protein. Caprin-1 and ubiquitin specific peptidase 10 (USP10) interact with G3BP1, facilitating and suppressing SG formation, respectively. The crystal structures of the nuclear transport factor 2-like (NTF2L) domain of G3BP1 in complex with the G3BP1-interacting motif (GIM) of Caprin-1 and USP10 show that both GIMs bind to the same hydrophobic pocket of G3BP1. Moreover, both GIMs suppressed the liquid-liquid phase separation (LLPS) of G3BP1, suggesting that Caprin-1 likely facilitates SG formation via other mechanisms. Thus, we dissected various domains of Caprin-1 and investigated their role in LLPS in vitro and SG formation in cells. The C-terminal domain of Caprin-1 underwent spontaneous LLPS, whereas the N-terminal domain and GIM of Caprin-1 suppressed LLPS of G3BP1. The opposing effect of the N- and C-terminal domains of Caprin-1 on SG formation were demonstrated in cells with or without the endogenous Caprin-1. We propose that the N- and C-terminal domains of Caprin-1 regulate SG formation in a "yin and yang" fashion, mediating the dynamic and reversible assembly of SGs.

Yin and yang regulation of stress granules by Caprin-1.,Song D, Kuang L, Yang L, Wang L, Li H, Li X, Zhu Z, Shi C, Zhu H, Gong W Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2207975119. doi: , 10.1073/pnas.2207975119. Epub 2022 Oct 24. PMID:36279435^[3]

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

References

↑ Costa M, Ochem A, Staub A, Falaschi A. Human DNA helicase VIII: a DNA and RNA helicase corresponding to the G3BP protein, an element of the ras transduction pathway. Nucleic Acids Res. 1999 Feb 1;27(3):817-21. PMID:9889278
↑ Tourriere H, Gallouzi IE, Chebli K, Capony JP, Mouaikel J, van der Geer P, Tazi J. RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization. Mol Cell Biol. 2001 Nov;21(22):7747-60. PMID:11604510 doi:10.1128/MCB.21.22.7747-7760.2001
↑ Song D, Kuang L, Yang L, Wang L, Li H, Li X, Zhu Z, Shi C, Zhu H, Gong W. Yin and yang regulation of stress granules by Caprin-1. Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2207975119. doi: , 10.1073/pnas.2207975119. Epub 2022 Oct 24. PMID:36279435 doi:http://dx.doi.org/10.1073/pnas.2207975119