Really excited that my first first-author paper (with @AtomicVirology) has been submitted and is available as a preprint on BioRxiv! Check it out: biorxiv.org/content/10.110…
#phdlife #AcademicChatter
I'll summarise the main findings in this thread (1/8)
#phdlife #AcademicChatter
I'll summarise the main findings in this thread (1/8)
@AtomicVirology The paper focuses on pUL7 and pUL51, conserved proteins from herpes simplex virus (HSV)-1 that form a complex required for efficient virus assembly. We used small-angle X-ray scattering with @svergungroup @embl Hamburg to characterise the complex in solution. (2/8) 
@AtomicVirology @svergungroup @embl We used X-ray crystallography to solve the atomic-resolution structure of the core pUL7:pUL51 heterodimer. pUL7 forms a single, compact, globular domain that is bound to pUL51, which forms an extended helix-turn-helix, via an extensive hydrophobic interface. (3/8)
@AtomicVirology @svergungroup @embl pUL7 adopts a previously-unseen fold, which we call the CUSTARD fold (Conserved UL7(Seven) Tegument Assembly/Release Domain). We present evidence that the CUSTARD fold is conserved across all herpesviruses. #CUSTARDfold (4/8)
@AtomicVirology @svergungroup @embl Mapping conservation of alphaherpesvirus sequences onto the crystal structure reveals several regions of conservation that overlap with the pUL7:pUL51 interface. We also present bioinformatic analyses suggesting that there is coevolution at the pUL7:pUL51 interface. (5/8)
@AtomicVirology @svergungroup @embl Using confocal microscopy, we show that homologues from other herpesvirus families co-localise with TGN46 at trans-Golgi membranes, providing further evidence that the pUL7:pUL51 complex is conserved across herpesviruses. Focal adhesion binding, however, is unique to HSV-1. (6/8)
@AtomicVirology @svergungroup @embl While pUL7 adopts a novel fold, pUL51 shows striking similarity to ESCRT-III components involved in cellular membrane remodelling. While ESCRT recruitment for virus budding is well established, structural mimicry of ESCRT proteins has not previously been reported. (7/8)
@AtomicVirology @svergungroup @embl Finally, I owe enormous thanks to all those involved with this project, including my brilliant supervisor @AtomicVirology and all those who have supported me along the way including (but not limited to) @JanetDeaneLab @chillzaa @EllieDunstone (8/8) #phdlife #AcademicChatter
