Andy DeLaitsch

Thank you!

Huge thanks to Florian Klein's lab for this excellent collaboration and to the various lab members who provided so much help seeing this through!

Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bnAb for HIV-1 prevention and therapy - Nature Immunology Klein and colleagues characterize 04_A06, a new VH1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.

All these antibodies exhibit canonical gp120 interactions made by CD4 and CD4bs bNAbs. Interestingly, the VH1-2-encoded N58 is mutated to K58 in the best of these bNAbs, which mimics interactions made between K35 of CD4 and gp120. www.nature.com/articles/s41...

The third bNAb, 05_B08, does not have any insertions and does not contact the adjacent gp120. This antibody, exhibited just over 50% breadth, which is much lower than the others.

Another of the bNAbs, 01_D03, has two separate insertions and a 20-residue long CDRH3, which together allow it to contact conserved residues on the adjacent gp120. This antibody has a 4-residue long FWRH3 insertion in the same location as a 4-residue insertion in 3BNC60/3BNC117.

Interestingly, a crystal structure of this antibody alone revealed this protruding loop was pre-organized for binding, which is expected to lower the entropic cost for binding.

These bNAbs differ in the length and position of insertions. The best-in-class bNAb, 04_A06, has an 11-residue long FWRH1 insertion which manifests in a long CDRH1 that reaches over to contact highly conserved residues on the adjacent gp120.

a, Schematics illustrating the position and length of FWRH1 and/or FWRH3 insertions of 04_A06 (left), 01_D03 (middle) and 05_B08 (right; top), EM maps showing side views of 04_A06, 01_D03 and 05_B08 bnAb Fabs in complex with BG505SOSIP.664 Env trimers (middle) and insets illustrating a close-up of bnAb interactions with the adjacent gp120 protomer (gp1202; bottom); HC, heavy chain; LC, light chain. b, Canonical interactions of CD4 and bnAbs to the CD4bs (04_A06, IOMA and VRC01) with Env gp120 D368, the F43 pocket and gp120 N280/R456. c, Interactions between the CDRH1s of 04_A06 (blue cartoon representation) and 1-18 (red cartoon representation) with the secondary (gp1202) Env protomer, shown as a surface colored by percent conservation. The inset (top right) shows the Env trimer–04_A06 complex as a surface representation for orientation. d, Crystal structure of unbound 04_A06 Fab (bottom) and inset highlighting the 04_A06 CDRH1, with electron density contoured at 1.5σ (top). e, Molecular surface representation showing the surface area buried by VRC01-class bnAbs (04_A06, 01_D03, 05_08, 3BNC117 and VRC01) on primary (gp1201) or secondary (gp1202) Env protomers (top). Listing of Protein Data Bank (PDB) accession codes, breadth (%), heavy chain insertion length and position, buried surface area (BSA) on gp1201 and gp1202 as well as total BSA for VRC01-class bnAbs (bottom).

There's a new best-in-class HIV-1 antibody out today! Happy to have contributed to the structural characterization of this, and two other distinct VRC01-class bNAbs isolated from a single individual. www.nature.com/articles/s41...

I second this bet.

And then Shankar Balasubramanian for chemistry.

From what I gather, CXCR4 (previously called fusin) was identified as a co-receptor for HIV nearly 30 years ago (pubmed.ncbi.nlm.nih.gov/8629022/). Nice to see a structure, and interesting to see it was done with HIV-2 gp120.

I am excited to share our new preprint on the CAGE complex, a mysterious hollow protein complex that I first saw years ago while surveying Tetrahymena ciliary lysate www.biorxiv.org/content/10.1... #cilia #protistsonsky 🧬🧪

Super cool!

📣 New paper alert! Just out in Cell Reports! pubmed.ncbi.nlm.nih.gov/40644298/
Thrilled to share that we have discovered a brand-new anti-phage defense system! Bacteria have evolved various defense strategies (CRISPR etc) to counter phage attacks. We found a new one - fascinating and dramatic
⚔️🦠❄️🔬

“On Being The Right Size” is a true classic, highly recommend! www.phys.ufl.edu/courses/phy3...

If Management is the Only Way Up, We're All F'd - Rand Fishkin
sparktoro.com/blog/if-mana...

In-situ structures of the Legionella Dot/Icm T4SS identify the DotA-IcmX complex as the gatekeeper for effector translocation The Dot/Icm machine in Legionella pneumophila is one of the most versatile type IV secretion systems (T4SSs), with a remarkable capacity to translocate over 330 different effector proteins across the ...

In-situ SPA 🧨

www.biorxiv.org/content/10.1...

Latest preprint from the lab, many years in the making!

By combining #cryoEM with #AlphaFold3 modelling, we propose that norovirus NS3 forms a transmembrane RNA translocase.

This could have big implications for our understanding of viral replication & assembly (🧵)

www.biorxiv.org/content/10.1...

Cool structure!

Cool demo! Also, it’s nice to see your IgG binds bivalently!

Instant classic 🤯

My first project in the @elowitzlab.bsky.social is finally out in @cellpress.bsky.social! We explore how competitive, "many-to-many" dimerization allows complex, multi-input, and cell-type-specific biochemical computations🧵↓

doi.org/10.1016/j.ce...

MISO: Microfluidic protein isolation enables single particle cryo-EM structure determination from a single cell colony https://www.biorxiv.org/content/10.1101/2025.01.10.632437v1

Infant RSV Vaccination Trouble

RSV vaccination attempts in young children have a troubled history. Which seems to be continuing:

For those interested: iubemcenter.indiana.edu/doc/ruska/ru...

100 years ago, De Broglie published his thesis, "On the Theory of Quanta". The ideas in it catalyzed the development of electron microscopy, though Ernst Ruska was apparently unaware of De Broglie's "material waves" when he and Max Knoll first started toying with the electron microscope.

That’s so cool!

Thank you!! 🎉

Neutralizing antibodies elicited in macaques recognize V3 residues on altered conformations of HIV-1 Env trimer - npj Vaccines npj Vaccines - Neutralizing antibodies elicited in macaques recognize V3 residues on altered conformations of HIV-1 Env trimer

Out now in its final form! These antibodies had us stumped for quite some time. www.nature.com/articles/s41...

Very excited to present the structural and mechanistic basis for stress response silencing by the monster E3 ligase SIFI.

www.biorxiv.org/content/10.1...

🙋‍♂️ Great list, thank you!