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- EMDB-64502: Structure of dimeric FKS1 in complex with tRNA -

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Basic information

Entry
Database: EMDB / ID: EMD-64502
TitleStructure of dimeric FKS1 in complex with tRNA
Map data
Sample
  • Complex: Dimeric Fks1 in complex with tRNA
    • Protein or peptide: x 2 types
    • RNA: x 1 types
  • Ligand: x 8 types
KeywordsMEMBRANE PROTEIN-RNA COMPLEX / MEMBRANE PROTEIN
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
1,3-beta-glucan synthase component FKS1 / Uncharacterized protein YMR295C
Similarity search - Component
Biological speciesSaccharomyces cerevisiae (brewer's yeast)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.96 Å
AuthorsLi JL / Zhu AQ / Liu JX / Dai XL / Wang X / Yan CY / Deng D
Funding support China, 1 items
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, 2025-
Header (metadata) releaseDec 17, 2025-
Map releaseDec 17, 2025-
UpdateDec 17, 2025-
Current statusDec 17, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_64502.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 400 pix.
= 440. Å
1.1 Å/pix.
x 400 pix.
= 440. Å
1.1 Å/pix.
x 400 pix.
= 440. Å

Surface

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Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-1.7817895 - 2.7500865
Average (Standard dev.)-0.00082054955 (±0.038321327)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 440.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_64502_msk_1.map
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Additional map: local refinement 1

Fileemd_64502_additional_1.map
Annotationlocal refinement 1
Projections & Slices
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Additional map: local refinement 2

Fileemd_64502_additional_2.map
Annotationlocal refinement 2
Projections & Slices
AxesZYX

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Half map: #1

Fileemd_64502_half_map_1.map
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Half map: #2

Fileemd_64502_half_map_2.map
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Sample components

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Entire : Dimeric Fks1 in complex with tRNA

EntireName: Dimeric Fks1 in complex with tRNA
Components
  • Complex: Dimeric Fks1 in complex with tRNA
    • Protein or peptide: Uncharacterized protein YMR295C
    • Protein or peptide: 1,3-beta-glucan synthase component FKS1
    • RNA: tRNA
  • Ligand: MAGNESIUM ION
  • Ligand: nonane
  • Ligand: DECANE
  • Ligand: HEPTANE
  • Ligand: (11R,14S)-17-amino-14-hydroxy-8,14-dioxo-9,13,15-trioxa-14lambda~5~-phosphaheptadecan-11-yl decanoate
  • Ligand: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE
  • Ligand: PALMITIC ACID
  • Ligand: icosanoic acid

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Supramolecule #1: Dimeric Fks1 in complex with tRNA

SupramoleculeName: Dimeric Fks1 in complex with tRNA / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Saccharomyces cerevisiae (brewer's yeast)

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Macromolecule #1: Uncharacterized protein YMR295C

MacromoleculeName: Uncharacterized protein YMR295C / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Saccharomyces cerevisiae (brewer's yeast)
Molecular weightTheoretical: 22.209684 KDa
SequenceString: MMHFRKKSSI SNTSDHDGAN RASDVKISED DKARLKMRTA SVADPILDAV QEAQPFEQAA DTFHDNMNRQ SYFSNEEGHV LCDVFGQPI TQADISNPTR ARDERPLDTI RSFEYAVSGD PVWAQQLETP TYGFRVRPDF PVFGAAVTYD ANGMPQQVGG A SSQMYGEQ ...String:
MMHFRKKSSI SNTSDHDGAN RASDVKISED DKARLKMRTA SVADPILDAV QEAQPFEQAA DTFHDNMNRQ SYFSNEEGHV LCDVFGQPI TQADISNPTR ARDERPLDTI RSFEYAVSGD PVWAQQLETP TYGFRVRPDF PVFGAAVTYD ANGMPQQVGG A SSQMYGEQ AVYQPQQHVQ TEEKQKKKKK GLFGRMKKK

UniProtKB: Uncharacterized protein YMR295C

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Macromolecule #2: 1,3-beta-glucan synthase component FKS1

MacromoleculeName: 1,3-beta-glucan synthase component FKS1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: 1,3-beta-glucan synthase
Source (natural)Organism: Saccharomyces cerevisiae (brewer's yeast)
Molecular weightTheoretical: 215.076156 KDa
SequenceString: MNTDQQPYQG QTDYTQGPGN GQSQEQDYDQ YGQPLYPSQA DGYYDPNVAA GTEADMYGQQ PPNESYDQDY TNGEYYGQPP NMAAQDGEN FSDFSSYGPP GTPGYDSYGG QYTASQMSYG EPNSSGTSTP IYGNYDPNAI AMALPNEPYP AWTADSQSPV S IEQIEDIF ...String:
MNTDQQPYQG QTDYTQGPGN GQSQEQDYDQ YGQPLYPSQA DGYYDPNVAA GTEADMYGQQ PPNESYDQDY TNGEYYGQPP NMAAQDGEN FSDFSSYGPP GTPGYDSYGG QYTASQMSYG EPNSSGTSTP IYGNYDPNAI AMALPNEPYP AWTADSQSPV S IEQIEDIF IDLTNRLGFQ RDSMRNMFDH FMVLLDSRSS RMSPDQALLS LHADYIGGDT ANYKKWYFAA QLDMDDEIGF RN MSLGKLS RKARKAKKKN KKAMEEANPE DTEETLNKIE GDNSLEAADF RWKAKMNQLS PLERVRHIAL YLLCWGEANQ VRF TAECLC FIYKCALDYL DSPLCQQRQE PMPEGDFLNR VITPIYHFIR NQVYEIVDGR FVKRERDHNK IVGYDDLNQL FWYP EGIAK IVLEDGTKLI ELPLEERYLR LGDVVWDDVF FKTYKETRTW LHLVTNFNRI WVMHISIFWM YFAYNSPTFY THNYQ QLVD NQPLAAYKWA SCALGGTVAS LIQIVATLCE WSFVPRKWAG AQHLSRRFWF LCIIFGINLG PIIFVFAYDK DTVYST AAH VVAAVMFFVA VATIIFFSIM PLGGLFTSYM KKSTRRYVAS QTFTAAFAPL HGLDRWMSYL VWVTVFAAKY SESYYFL VL SLRDPIRILS TTAMRCTGEY WWGAVLCKVQ PKIVLGLVIA TDFILFFLDT YLWYIIVNTI FSVGKSFYLG ISILTPWR N IFTRLPKRIY SKILATTDME IKYKPKVLIS QVWNAIIISM YREHLLAIDH VQKLLYHQVP SEIEGKRTLR APTFFVSQD DNNFETEFFP RDSEAERRIS FFAQSLSTPI PEPLPVDNMP TFTVLTPHYA ERILLSLREI IREDDQFSRV TLLEYLKQLH PVEWECFVK DTKILAEETA AYEGNENEAE KEDALKSQID DLPFYCIGFK SAAPEYTLRT RIWASLRSQT LYRTISGFMN Y SRAIKLLY RVENPEIVQM FGGNAEGLER ELEKMARRKF KFLVSMQRLA KFKPHELENA EFLLRAYPDL QIAYLDEEPP LT EGEEPRI YSALIDGHCE ILDNGRRRPK FRVQLSGNPI LGDGKSDNQN HALIFYRGEY IQLIDANQDN YLEECLKIRS VLA EFEELN VEQVNPYAPG LRYEEQTTNH PVAIVGAREY IFSENSGVLG DVAAGKEQTF GTLFARTLSQ IGGKLHYGHP DFIN ATFMT TRGGVSKAQK GLHLNEDIYA GMNAMLRGGR IKHCEYYQCG KGRDLGFGTI LNFTTKIGAG MGEQMLSREY YYLGT QLPV DRFLTFYYAH PGFHLNNLFI QLSLQMFMLT LVNLSSLAHE SIMCIYDRNK PKTDVLVPIG CYNFQPAVDW VRRYTL SIF IVFWIAFVPI VVQELIERGL WKATQRFFCH LLSLSPMFEV FAGQIYSSAL LSDLAIGGAR YISTGRGFAT SRIPFSI LY SRFAGSAIYM GARSMLMLLF GTVAHWQAPL LWFWASLSSL IFAPFVFNPH QFAWEDFFLD YRDYIRWLSR GNNQYHRN S WIGYVRMSRA RITGFKRKLV GDESEKAAGD ASRAHRTNLI MAEIIPCAIY AAGCFIAFTF INAQTGVKTT DDDRVNSVL RIIICTLAPI AVNLGVLFFC MGMSCCSGPL FGMCCKKTGS VMAGIAHGVA VIVHIAFFIV MWVLESFNFV RMLIGVVTCI QCQRLIFHC MTALMLTREF KNDHANTAFW TGKWYGKGMG YMAWTQPSRE LTAKVIELSE FAADFVLGHV ILICQLPLII I PKIDKFHS IMLFWLKPSR QIRPPIYSLK QTRLRKRMVK KYCSLYFLVL AIFAGCIIGP AVASAKIHKH IGDSLDGVVH NL FQPINTT NNDTGSQMST YQSHYYTHTP SLKTWSTIK

UniProtKB: 1,3-beta-glucan synthase component FKS1

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Macromolecule #3: tRNA

MacromoleculeName: tRNA / type: rna / ID: 3 / Number of copies: 1
Source (natural)Organism: Saccharomyces cerevisiae (brewer's yeast)
Molecular weightTheoretical: 24.503461 KDa
SequenceString:
GGGCGUGUGG CGUAGUCGGU AGCGCGCUCC CUUIGCAUGG GAGAGGUCUC CGGUUCGAUU CCGGACUCGU CCGCCA

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Macromolecule #6: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: MG
Molecular weightTheoretical: 24.305 Da

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Macromolecule #7: nonane

MacromoleculeName: nonane / type: ligand / ID: 7 / Number of copies: 8 / Formula: DD9
Molecular weightTheoretical: 128.255 Da
Chemical component information

ChemComp-DD9:
nonane

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Macromolecule #8: DECANE

MacromoleculeName: DECANE / type: ligand / ID: 8 / Number of copies: 2 / Formula: D10
Molecular weightTheoretical: 142.282 Da
Chemical component information

ChemComp-D10:
DECANE

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Macromolecule #9: HEPTANE

MacromoleculeName: HEPTANE / type: ligand / ID: 9 / Number of copies: 6 / Formula: HP6
Molecular weightTheoretical: 100.202 Da
Chemical component information

ChemComp-HP6:
HEPTANE

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Macromolecule #10: (11R,14S)-17-amino-14-hydroxy-8,14-dioxo-9,13,15-trioxa-14lambda~...

MacromoleculeName: (11R,14S)-17-amino-14-hydroxy-8,14-dioxo-9,13,15-trioxa-14lambda~5~-phosphaheptadecan-11-yl decanoate
type: ligand / ID: 10 / Number of copies: 2 / Formula: XKP
Molecular weightTheoretical: 495.587 Da
Chemical component information

ChemComp-XKP:
(11R,14S)-17-amino-14-hydroxy-8,14-dioxo-9,13,15-trioxa-14lambda~5~-phosphaheptadecan-11-yl decanoate

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Macromolecule #11: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE

MacromoleculeName: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / type: ligand / ID: 11 / Number of copies: 2 / Formula: PEF
Molecular weightTheoretical: 691.959 Da
Chemical component information

ChemComp-PEF:
DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / phospholipid*YM

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Macromolecule #12: PALMITIC ACID

MacromoleculeName: PALMITIC ACID / type: ligand / ID: 12 / Number of copies: 16 / Formula: PLM
Molecular weightTheoretical: 256.424 Da
Chemical component information

ChemComp-PLM:
PALMITIC ACID

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Macromolecule #13: icosanoic acid

MacromoleculeName: icosanoic acid / type: ligand / ID: 13 / Number of copies: 2 / Formula: DCR
Molecular weightTheoretical: 312.53 Da
Chemical component information

ChemComp-DCR:
icosanoic acid

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.1 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.96 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 243849
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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