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Abraham lab at Harvard Medical School

@abrahamlabhms.bsky.social
148 followers 185 following 64 posts
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 16/09/2026
We further determined a structure of the primase-polymerase core complex in a state that likely occurs during the synthesis of RNA primers.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 16/09/2026
The structures reveal that after binding to the polymerase, a conformational change in the E5 helicase-primase exposes the helicase ssDNA channel, activating the helicase. Single-molecule optical tweezers experiments done with @joeloparo.bsky.social confirmed this activation mechanism.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 16/09/2026
We determined high-resolution cryo-EM structures of the MPXV hexameric E5 helicase-primase bound to the polymerase complex bound to DNA 🧬. The structures capture both of these key viral proteins in action.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 25/08/2026
Lysine residues are often critical for ligand interactions with LDLR receptors. We identify lysine residues that are important for receptor binding in the yellow fever virus and tick-borne encephalitis virus E proteins.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 25/08/2026
Our structural analysis also revealed that tick-borne encephalitis virus binds LA repeats 1-2 interact LRP8 but uses domain II of its E protein, while yellow fever virus uses domains I and III.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 25/08/2026
We determined cryo-EM structures of yellow fever virus in complex with either LRP4 or LRP8. LA repeats in these receptors bind viruses and ligands. Yellow fever virus binds LRP4 LA repeats 6 and 7 (6,7!!!😂), or LRP8 LA repeats 1 and 2.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 25/08/2026
We are excited to share our new @biorxivpreprint.bsky.social examining the structural basis for receptor binding by two flaviviruses 🤩: www.biorxiv.org/content/10.6... @harvardmicro.bsky.social @harvardvirology.bsky.social @hhmi-science.bsky.social
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 30/07/2026
Previous studies showed that Semliki Forest virus (SFV) binds the human receptor VLDLR on the E1 glycoprotein, leaving the canonical receptor binding clefts conspicuously empty 🤔 We were scratching our heads until we saw that SFV actually uses its clefts to bind the mosquito receptor Lachesin!
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 30/07/2026
We used cryo-EM at @hc2em.bsky.social to visualize how alphaviruses bind the mosquito receptor. Lachesin binds within the cleft of adjacent E2–E1 heterodimers, which is also a site where CHIKV binds MXRA8, a receptor on human cells.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 30/07/2026
Related alphaviruses including Mayaro virus and Ross River viruses use Lachesin as a receptor. Multiple alphaviruses recognize diverse mosquito orthologs of Lachesin, suggesting that receptor binding is not a major barrier to mosquito vector specificity.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 30/07/2026
Working with @perrimonlab.bsky.social we performed a CRISPR-Cas9 screen in mosquito cells and identified Lachesin as a CHIKV receptor. Lachesin is a GPI-anchored protein in contrast to other known alphavirus receptors, which all have a transmembrane domain.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 30/07/2026
We are excited to share two preprints reporting a mosquito-specific receptor for chikungunya virus and other alphaviruses! 🤩 www.biorxiv.org/content/10.6... www.biorxiv.org/content/10.6... @harvardmicro.bsky.social @harvardvirology.bsky.social @hhmi-science.bsky.social
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 29/12/2025
We also show that helicase residue K356 plays a key role in stabilizing HPI binding to the HSV-1 H/P complex. UL52 residues used in drug binding are poorly conserved across β- and γ-herpesviruses, a possible explanation for α-herpesvirus drug specificity.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 29/12/2025
We discovered an extensive interface between polymerase (UL30) and helicase (UL5), mediated in part by a conserved motif within the polymerase.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 29/12/2025
Cryo-EM maps of H/P subunits UL5, UL52, and UL8 reveal a bilobed architecture centered on primase UL52. Further addition of the polymerase holoenzyme UL30 and UL42 allowed us to understand how the HSV-1 replication fork assembles onto DNA and its inhibition by HPI drugs.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 29/12/2025
We are excited to share our new @CellCellPress paper revealing mechanisms of action of promising drugs against the helicase-primase of herpes simplex virus 1 (HSV-1) 🤩 harvardvirology.bsky.social www.cell.com/cell/fulltex...
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 09/08/2025
A K33A substitution in the stable signal peptide (SSP) allowed for stabilization of the pre-fusion GPC, with molecular dynamics suggesting K33A stabilizes GPC by better accommodating membrane lipids in the SSP33 pocket, supported by our cryo-EM density
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 09/08/2025
Further structural and functional analyses also reveal the effect of specific residues in transmembrane and membrane proximal region on pH-mediated fusion, elucidating the attenuation mechanism of the JUNV Candid#1 vaccine
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 09/08/2025
These cryo-EM structures reveal notable differences between JUNV and MACV in GP1 organization at the apex and C terminus. The MACV GPC apex has a more open appearance due to its GP1 subunits slightly rotating outwards and clockwise 🔃compared to JUNV GP1 subunits
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 09/08/2025
Our @natmicrobiol.nature.com paper provides the most complete insight into the molecular organization of the JUNV and MACV GPCs yet 😲revealing new features not seen in previous structures, such as the TM helices and cytosolic portions, including ZBD
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 04/04/2025
Interesting tidbit in the story: a WEEV-related alphavirus that circulates on the east coast (EEEV territory) called highlands J virus (HJV) also uses PCDH10 as a receptor. It diverged from WEEV not that long ago and retained most PCDH10 contact residues.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 04/04/2025
Some WEEV strains and EEEV both bind VLDLR at the LA1 and LA2 domains, suggesting that VLDLR LA1-LA2 decoy receptor may have broad activity against them. This molecule protected mice against lethal challenge by a WEEV strain that binds VLDLR.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 04/04/2025
Strains isolated during epidemics of the early 20th century bind VLDLR and ApoER2 as additional receptors. Our structure of a 1941 strain bound by VLDLR revealed a distinct binding mode than other alphaviruses that bind LDLR-related proteins, such as EEEV, SFV or VEEV.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 04/04/2025
We found a substitution in the E2 glycoprotein, L149Q, that would disrupt hydrophobic contact with PCDH10, and confirmed this mutation alone abolishes human PCDH10 binding. L149Q is found in all strains isolated in California and Texas in 2005, suggesting a wide geographic range.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 04/04/2025
Protocadherin 10 (PCDH10) is a major receptor for WEEV. Multiple strains isolated in 2005 lost the ability to bind human and horse PCDH10, yet still bind avian PCDH10. Cryo-EM structures show identical binding mode of sparrow and human PCDH10.
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 02/01/2025
We also determined structures of an ancestral WEEV strain bound to VLDLR, revealing a distinct binding mode compared to other alphaviruses that bind LDLR-related receptors such as EEEV, SFV, or VEEV, indicating independent evolution of WEEV to bind VLDLR/ApoER2!
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Abraham lab at Harvard Medical School @abrahamlabhms.bsky.social · 02/01/2025
Excited to share our @biorxivpreprint.bsky.social exploring how binding of western equine encephalitis virus (WEEV) to its cellular receptors evolved over the past century 🤩 www.biorxiv.org/content/10.1... @harvardmicro.bsky.social
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