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- PDB-9utw: Structure of dimeric FKS1 in complex with tRNA -

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Basic information

Entry
Database: PDB / ID: 9utw
TitleStructure of dimeric FKS1 in complex with tRNA
Components
  • 1,3-beta-glucan synthase component FKS1
  • Uncharacterized protein YMR295C
  • tRNA
KeywordsMEMBRANE PROTEIN / MEMBRANE PROTEIN-RNA COMPLEX
Function / homology
Function and homology information


regulation of cell wall (1->3)-beta-D-glucan biosynthetic process / fungal-type cell wall polysaccharide biosynthetic process / 1,3-beta-glucan synthase / 1,3-beta-D-glucan synthase activity / (1->3)-beta-D-glucan biosynthetic process / 1,3-beta-D-glucan synthase complex / fungal-type cell wall biogenesis / cellular bud / ascospore wall assembly / actin cortical patch ...regulation of cell wall (1->3)-beta-D-glucan biosynthetic process / fungal-type cell wall polysaccharide biosynthetic process / 1,3-beta-glucan synthase / 1,3-beta-D-glucan synthase activity / (1->3)-beta-D-glucan biosynthetic process / 1,3-beta-D-glucan synthase complex / fungal-type cell wall biogenesis / cellular bud / ascospore wall assembly / actin cortical patch / cellular bud tip / fungal-type cell wall / cellular bud neck / mating projection tip / regulation of cell size / positive regulation of endocytosis / cell periphery / mitochondrion / plasma membrane
Similarity search - Function
Protein of unknown function DUF2406 / Uncharacterised protein (DUF2406) / : / 1,3-beta-glucan synthase component FKS1, second domain / Glycosyl transferase, family 48 / 1,3-beta-glucan synthase subunit FKS1-like, domain-1 / 1,3-beta-glucan synthase component / 1,3-beta-glucan synthase subunit FKS1, domain-1 / 1,3-beta-glucan synthase subunit FKS1
Similarity search - Domain/homology
beta-laminaribiose / DECANE / icosanoic acid / nonane / HEPTANE / DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / PALMITIC ACID / Chem-XKP / RNA / RNA (> 10) ...beta-laminaribiose / DECANE / icosanoic acid / nonane / HEPTANE / DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / PALMITIC ACID / Chem-XKP / RNA / RNA (> 10) / 1,3-beta-glucan synthase component FKS1 / Uncharacterized protein YMR295C
Similarity search - Component
Biological speciesSaccharomyces cerevisiae (brewer's yeast)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.96 Å
AuthorsLi, J.L. / Zhu, A.Q. / Liu, J.X. / Dai, X.L. / Wang, X. / Yan, C.Y. / Deng, D.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2025
Title: Structural-guided identification of two modulators of β-1,3-glucan synthase FKS1.
Authors: Jialu Li / Jian Li / Angqi Zhu / Xinli Dai / Juxiu Liu / Huayi Liu / Zhili Xia / Yuefan Dong / Wenyu Qian / Lunzhi Dai / Li Guo / Chuangye Yan / Dong Deng / Yunzi Luo / Xiang Wang /
Abstract: FKS1 is a β-1,3-glucan synthase critical for fungal cell wall formation and a target for antifungal drugs such as echinocandin and ibrexafungerp. However, the mechanisms regulating FKS1 activity ...FKS1 is a β-1,3-glucan synthase critical for fungal cell wall formation and a target for antifungal drugs such as echinocandin and ibrexafungerp. However, the mechanisms regulating FKS1 activity remain largely unknown. Here, we reveal that transfer RNA (tRNA) acts as an endogenous inhibitor, whereas GSR1 functions as a stabilizer of FKS1. The cryo-EM structure of FKS1 adopts a tRNA-mediated homodimer configuration, representing a quiescent state of β-1,3-glucan synthase. Unexpectedly, the copurified endogenous tRNA is identified as a potent inhibitor that suppresses FKS1 activity. Moreover, high-resolution cryo-EM density analysis enable the identification of GSR1 as an additional binding partner of FKS1. Mutagenesis experiments confirm the interaction between FKS1 and GSR1. Evolutionarily conserved GSR1 is found to increase the stability of FKS1 in β-1,3-glucan biosynthesis. Collectively, our findings identify both tRNA and GSR1 as intrinsic modulators of β-1,3-glucan biosynthesis, thereby providing opportunities for the further development of FKS1-targeted antifungal drugs.
History
DepositionMay 5, 2025Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 17, 2025Provider: repository / Type: Initial release
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
C: Uncharacterized protein YMR295C
G: Uncharacterized protein YMR295C
H: 1,3-beta-glucan synthase component FKS1
B: 1,3-beta-glucan synthase component FKS1
A: tRNA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)508,98547
Polymers499,0755
Non-polymers9,91042
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 2 types, 4 molecules CGHB

#1: Protein Uncharacterized protein YMR295C


Mass: 22209.684 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: Q03559
#2: Protein 1,3-beta-glucan synthase component FKS1 / 1 / 3-beta-D-glucan-UDP glucosyltransferase / Calcineurin dependent protein 1 / Calcofluor white ...1 / 3-beta-D-glucan-UDP glucosyltransferase / Calcineurin dependent protein 1 / Calcofluor white hypersensitivity protein 53 / Echinocandin target gene protein 1 / FK506 sensitivity protein 1 / Glucan synthase of cerevisiae protein 1 / Papulacandin B resistance protein 1


Mass: 215076.156 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: P38631, 1,3-beta-glucan synthase

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RNA chain , 1 types, 1 molecules A

#3: RNA chain tRNA


Mass: 24503.461 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast)

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Sugars , 2 types, 2 molecules

#4: Polysaccharide beta-D-glucopyranose-(1-3)-beta-D-glucopyranose-(1-3)-beta-D-glucopyranose


Type: oligosaccharide / Mass: 504.438 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpb1-3DGlcpb1-3DGlcpb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,3,2/[a2122h-1b_1-5]/1-1-1/a3-b1_b3-c1WURCSPDB2Glycan 1.1.0
[][b-D-Glcp]{[(3+1)][b-D-Glcp]{[(3+1)][b-D-Glcp]{}}}LINUCSPDB-CARE
#5: Polysaccharide beta-D-glucopyranose-(1-3)-beta-D-glucopyranose


Type: oligosaccharide, Oligosaccharide / Class: Antimicrobial / Mass: 342.297 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: oligosaccharide / References: beta-laminaribiose
DescriptorTypeProgram
DGlcpb1-3DGlcpb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5]/1-1/a3-b1WURCSPDB2Glycan 1.1.0
[][b-D-Glcp]{[(3+1)][b-D-Glcp]{}}LINUCSPDB-CARE

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Non-polymers , 8 types, 40 molecules

#6: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#7: Chemical
ChemComp-DD9 / nonane


Mass: 128.255 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C9H20 / Feature type: SUBJECT OF INVESTIGATION
#8: Chemical ChemComp-D10 / DECANE


Mass: 142.282 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H22 / Feature type: SUBJECT OF INVESTIGATION
#9: Chemical
ChemComp-HP6 / HEPTANE


Mass: 100.202 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C7H16 / Feature type: SUBJECT OF INVESTIGATION
#10: Chemical ChemComp-XKP / (11R,14S)-17-amino-14-hydroxy-8,14-dioxo-9,13,15-trioxa-14lambda~5~-phosphaheptadecan-11-yl decanoate


Mass: 495.587 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H46NO8P / Feature type: SUBJECT OF INVESTIGATION
#11: Chemical ChemComp-PEF / DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / 3-[AMINOETHYLPHOSPHORYL]-[1,2-DI-PALMITOYL]-SN-GLYCEROL


Mass: 691.959 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C37H74NO8P / Feature type: SUBJECT OF INVESTIGATION / Comment: phospholipid*YM
#12: Chemical
ChemComp-PLM / PALMITIC ACID


Mass: 256.424 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: C16H32O2 / Feature type: SUBJECT OF INVESTIGATION
#13: Chemical ChemComp-DCR / icosanoic acid


Mass: 312.530 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H40O2 / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Dimeric Fks1 in complex with tRNA / Type: COMPLEX / Entity ID: #1-#3 / Source: NATURAL
Source (natural)Organism: Saccharomyces cerevisiae (brewer's yeast)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1100 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

CTF correctionType: NONE
3D reconstructionResolution: 2.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 243849 / Symmetry type: POINT

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