+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18212 | |||||||||
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Title | Cryo-EM structure of Adenovirus C5 hexon | |||||||||
Map data | ||||||||||
Sample |
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Keywords | capsid protein / trimer / VIRUS | |||||||||
Function / homology | Function and homology information T=25 icosahedral viral capsid / microtubule-dependent intracellular transport of viral material towards nucleus / host cell / viral capsid / symbiont entry into host cell / host cell nucleus / structural molecule activity Similarity search - Function | |||||||||
Biological species | Human adenovirus 5 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Zoll S / Dhillon A | |||||||||
Funding support | Czech Republic, 1 items
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Citation | Journal: J Virol / Year: 2024 Title: Structural insights into the interaction between adenovirus C5 hexon and human lactoferrin. Authors: Arun Dhillon / B David Persson / Alexander N Volkov / Hagen Sülzen / Alan Kádek / Petr Pompach / Sami Kereïche / Martin Lepšík / Katarina Danskog / Charlotte Uetrecht / Niklas Arnberg / Sebastian Zoll / Abstract: Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackie-adenovirus receptor (CAR) for attachment ...Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackie-adenovirus receptor (CAR) for attachment and subsequently integrins for entry. CAR and integrins are however located deep within the tight junctions in the mucosa where they would not be easily accessible. Recently, a model for CAR-independent AdV entry was proposed. In this model, human lactoferrin (hLF), an innate immune protein, aids the viral uptake into epithelial cells by mediating interactions between the major capsid protein, hexon, and yet unknown host cellular receptor(s). However, a detailed understanding of the molecular interactions driving this mechanism is lacking. Here, we present a new cryo-EM structure of HAdV-5C hexon at high resolution alongside a hybrid structure of HAdV-5C hexon complexed with human lactoferrin (hLF). These structures reveal the molecular determinants of the interaction between hLF and HAdV-C5 hexon. hLF engages hexon primarily its N-terminal lactoferricin (Lfcin) region, interacting with hexon's hypervariable region 1 (HVR-1). Mutational analyses pinpoint critical Lfcin contacts and also identify additional regions within hLF that critically contribute to hexon binding. Our study sheds more light on the intricate mechanism by which HAdV-C5 utilizes soluble hLF/Lfcin for cellular entry. These findings hold promise for advancing gene therapy applications and inform vaccine development. IMPORTANCE: Our study delves into the structural aspects of adenovirus (AdV) infections, specifically HAdV-C5 in the respiratory epithelium. It uncovers the molecular details of a novel pathway where ...IMPORTANCE: Our study delves into the structural aspects of adenovirus (AdV) infections, specifically HAdV-C5 in the respiratory epithelium. It uncovers the molecular details of a novel pathway where human lactoferrin (hLF) interacts with the major capsid protein, hexon, facilitating viral entry, and bypassing traditional receptors such as CAR and integrins. The study's cryo-EM structures reveal how hLF engages hexon, primarily through its N-terminal lactoferricin (Lfcin) region and hexon's hypervariable region 1 (HVR-1). Mutational analyses identify critical Lfcin contacts and other regions within hLF vital for hexon binding. This structural insight sheds light on HAdV-C5's mechanism of utilizing soluble hLF/Lfcin for cellular entry, holding promise for gene therapy and vaccine development advancements in adenovirus research. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18212.map.gz | 51.2 MB | EMDB map data format | |
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Header (meta data) | emd-18212-v30.xml emd-18212.xml | 13.9 KB 13.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18212_fsc.xml | 9.9 KB | Display | FSC data file |
Images | emd_18212.png | 45.1 KB | ||
Filedesc metadata | emd-18212.cif.gz | 5.4 KB | ||
Others | emd_18212_half_map_1.map.gz emd_18212_half_map_2.map.gz | 95.7 MB 95.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18212 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18212 | HTTPS FTP |
-Validation report
Summary document | emd_18212_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_18212_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_18212_validation.xml.gz | 18.2 KB | Display | |
Data in CIF | emd_18212_validation.cif.gz | 23.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18212 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18212 | HTTPS FTP |
-Related structure data
Related structure data | 8q7cMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18212.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.828 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_18212_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_18212_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Ternary complex of adenovirus C5 hexon polypeptides
Entire | Name: Ternary complex of adenovirus C5 hexon polypeptides |
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Components |
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-Supramolecule #1: Ternary complex of adenovirus C5 hexon polypeptides
Supramolecule | Name: Ternary complex of adenovirus C5 hexon polypeptides / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Human adenovirus 5 |
Molecular weight | Theoretical: 324 KDa |
-Macromolecule #1: Hexon protein
Macromolecule | Name: Hexon protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human adenovirus 5 |
Molecular weight | Theoretical: 108.107617 KDa |
Sequence | String: MATPSMMPQW SYMHISGQDA SEYLSPGLVQ FARATETYFS LNNKFRNPTV APTHDVTTDR SQRLTLRFIP VDREDTAYSY KARFTLAVG DNRVLDMAST YFDIRGVLDR GPTFKPYSGT AYNALAPKGA PNPCEWDEAA TALEINLEEE DDDNEDEVDE Q AEQQKTHV ...String: MATPSMMPQW SYMHISGQDA SEYLSPGLVQ FARATETYFS LNNKFRNPTV APTHDVTTDR SQRLTLRFIP VDREDTAYSY KARFTLAVG DNRVLDMAST YFDIRGVLDR GPTFKPYSGT AYNALAPKGA PNPCEWDEAA TALEINLEEE DDDNEDEVDE Q AEQQKTHV FGQAPYSGIN ITKEGIQIGV EGQTPKYADK TFQPEPQIGE SQWYETEINH AAGRVLKKTT PMKPCYGSYA KP TNENGGQ GILVKQQNGK LESQVEMQFF STTEATAGNG DNLTPKVVLY SEDVDIETPD THISYMPTIK EGNSRELMGQ QSM PNRPNY IAFRDNFIGL MYYNSTGNMG VLAGQASQLN AVVDLQDRNT ELSYQLLLDS IGDRTRYFSM WNQAVDSYDP DVRI IENHG TEDELPNYCF PLGGVINTET LTKVKPKTGQ ENGWEKDATE FSDKNEIRVG NNFAMEINLN ANLWRNFLYS NIALY LPDK LKYSPSNVKI SDNPNTYDYM NKRVVAPGLV DCYINLGARW SLDYMDNVNP FNHHRNAGLR YRSMLLGNGR YVPFHI QVP QKFFAIKNLL LLPGSYTYEW NFRKDVNMVL QSSLGNDLRV DGASIKFDSI CLYATFFPMA HNTASTLEAM LRNDTND QS FNDYLSAANM LYPIPANATN VPISIPSRNW AAFRGWAFTR LKTKETPSLG SGYDPYYTYS GSIPYLDGTF YLNHTFKK V AITFDSSVSW PGNDRLLTPN EFEIKRSVDG EGYNVAQCNM TKDWFLVQML ANYNIGYQGF YIPESYKDRM YSFFRNFQP MSRQVVDDTK YKDYQQVGIL HQHNNSGFVG YLAPTMREGQ AYPANFPYPL IGKTAVDSIT QKKFLCDRTL WRIPFSSNFM SMGALTDLG QNLLYANSAH ALDMTFEVDP MDEPTLLYVL FEVFDVVRVH RPHRGVIETV YLRTPFSAGN ATT UniProtKB: Hexon protein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K2 IS (4k x 4k) / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |