Krishna Reddy

Krishna Reddy

@krishnareddy.bsky.social

Assistant Professor, University of South Florida. Membrane protein structure-function, engineering, evolution. My beard hides several personality flaws.

99 followers123 following21 posts

Krishna Reddy reposted

Chris Mulligan
@chrismulligan.bsky.social

🚨My lab is hiring a postdoc!🚨 If you’re interested in working out the mechanism and physiological impact of bacterial lipid transport processes then please apply! Job advert is here: tinyurl.com/4swddfda Get in touch by email (c.mulligan@kent.ac.uk) for informal enquiries Please repost! Thanks!

Krishna Reddy
@krishnareddy.bsky.social

My lab is hiring a postdoc! We have many exciting projects on membrane transporters at the interface of protein structure-function, bioinformatics, directed evolution, and protein engineering. Applications considered on a rolling basis, so submit ASAP. Please share! jobs.usf.edu/hcmUI/Candid...

jobs.usf.eduPostdoctoral Scholar ResearchThe Reddy Lab at the University of South Florida (USF) is seeking a Postdoctoral Researcher to join our multidisciplinary team studying the structure, mechanism, evolution, and engineering of membrane...
Krishna Reddy
@krishnareddy.bsky.social

Our department is recruiting a mid-career faculty member in cryo-EM - come be my colleague and lab neighbor! It's an exciting time for structural biology at USF, anchored by an incoming JEOL CRYOARM 300. Feel free to DM if you have any questions. Please share! www.nature.com/naturecareer...

nature.comASSOCIATE/FULL PROFESSOR - Open Rank-Structural Biology - Tampa, Florida job with University of South Florida | 12849234Seeking candidates for a tenured or tenure-track position who use structural biology-based approaches and cryo-EM
Krishna Reddy
@krishnareddy.bsky.social

So cool to have a spotlight on our work like this - honestly as good an alternative to reading the paper itself, which I probably shouldn't say...and also stay tuned for cool transporter evolution work from Sam 👀

Sam Berry@sberry.bsky.social

This is a very cool ancestral reconstruction study by @krishnareddy.bsky.social et al. that I recommend reading! @rachellegaudet.bsky.social and I thought it was so interesting that we wrote a News & Views about it, check it out: rdcu.be/eCfyl

rdcu.beA structural window into the evolution of secondary transport mechanismsNature Structural & Molecular Biology - Protein sequence signatures suggest that eons ago, a bacterial glutamate transporter lost its sodium coupling to make way for a shift to proton coupling....
Krishna Reddy
@krishnareddy.bsky.social

14/14 If you’ve made it this far, I really appreciate it (and also go touch grass). My lab is pushing this work in new directions and incorporating more fun, interdisciplinary techniques to understand transporter structure-function mechanism in unique ways. If this sounds interesting, reach out!

Krishna Reddy
@krishnareddy.bsky.social

11/14 This means ion coupling isn’t solely dictated by ion-binding residues, but from allosterically regulated packing - a structural “clutch” linking ion/substrate binding. We think this applies to ion-coupled transport and beyond - small, distant mutations can flip fundamental energy landscapes.

Krishna Reddy
@krishnareddy.bsky.social

12/14 There are a lot of interesting implications and future directions we are pursuing in my lab, beautifully summarized by @sberry.bsky.social @rachellegaudet.bsky.social in a @natsmb.nature.com News & Views article, freely available below. rdcu.be/eDRcX

rdcu.beA structural window into the evolution of secondary transport mechanismsNature Structural & Molecular Biology - Protein sequence signatures suggest that eons ago, a bacterial glutamate transporter lost its sodium coupling to make way for a shift to proton coupling....
Krishna Reddy
@krishnareddy.bsky.social

9/14 Cryo-EM with precise sample conditions and processing gave us the clue: the intermediate ancestor could spontaneously access the high-affinity substrate-binding state required for transport, which sodium-coupled transporters can only reach with sodium.

Krishna Reddy
@krishnareddy.bsky.social

10/14 What changed? Our evolutionary analysis gave us an elegant answer. A central ‘coupling’ helix is responsible for cooperative ion/substrate binding, and two changes at the start and end of this helix can turn sodium coupling on/off. These residues control how rigidly the helices pack together.

Krishna Reddy
@krishnareddy.bsky.social

7/14 Our ancestral membrane proteins had terrible yields, making purification/characterization a pain. We reinvented all the lab pipelines to make this project work. I like to call this the protein purification of Theseus. If you replace every step of a protocol, is it the same protocol? 🤔

Krishna Reddy
@krishnareddy.bsky.social

8/14 To our surprise, an ‘intermediate’ ancestor during the transition from sodium to proton coupling still had sodium binding sites, could bind sodium, but no longer needed sodium energy for substrate binding and transport - an ion-independent, ‘uncoupled’ transporter. How?

Krishna Reddy
@krishnareddy.bsky.social

3/14 Brain glutamate transporters use sodium to recycle neurotransmitters. Close relatives in bacteria also use sodium…but others use protons. We wanted to understand how transporters made this switch. What changes in sequence made this possible? And what molecular features enforce ion coupling?

Krishna Reddy
@krishnareddy.bsky.social

2/14 Secondary active transporters perform ‘concentrative’ transport, moving substrates against their concentration gradients by harnessing energy from ion gradients. Organisms have evolved their transporters based on their environment – i.e., halophiles often have sodium-driven transporters.

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