Publications

TL;DR In this work, we confirm theoretical predications that microscope aberrations can be corrected in determining single particle cryo-EM structures. Previous studies on well-aligned instruments showed this was possible, but we wanted to know the extent of aberration correction on lower electron energy instruments that weren't perfectly aligned. Using latest developments in RELION, we improved the resolution of our data from 4.9Å to 2.8Å. We feel better knowing it's possible to correct microscope-induced aberrations by a significant degree!

TL;DR Single particle cryo-EM requires a number of subjective user decisions before you get to 3D structure determination. At the core of this is data interpretation as 'good' or 'bad' for micrographs and 2D class averages. To automate these 'pre-processing' steps, we trained deep-learning neural networks to automatically assess cryoEM to enable pre-processing of data without user intervention.

Highlighted:

• Automating Decision Making in the Cryo-EM Pre-processing Pipeline. K. Maruthi, M. Kopylov, B. Carragher. Structure . 2020 Jul 7;28(7):727-729.

TL;DR Here, in collaboration with Dr. Bill Tsai's lab at U-M, we determine that the dynein adaptor BicD2 directly uncoats SV40 in vitro. SV40 is a non-enveloped virus that must make its way to the nucleus in order to express its DNA genome. During this process, SV40 utilizes dynein, although the extract role that dynein plays was unclear. Surprisingly, we found that BicD2 facilitates viral disassembly, suggesting that SV40 may utilize the dynein adaptor BicD2 to couple crossing of the endoplasmic reticulum membrane with disassembly.

TL;DR In our first review article on Miro, we summarize the current understanding of the outer-mitochondrial membrane protein, Miro, and its interactions with motors and binding partners, its biochemical features, and its structure.

TL;DR In collaboration with Dr. Liz Kellogg (Cornell University), we wrote a review targeted at new users in cryoEM to help them get-up-to-speed with sample preparation, analysis, and structure determination.

TL;DR In a tour de force, Jen pushed through many cryoEM and atomic model building hurdles to determine the first structure of P-Rex1, a Rho-guanine exchange factor (RhoGEF). Surprisingly, P-Rex1 adopts a completely compact structure with interwoven domains that were previously thought to be 'beads-on-a-string.' We also discovered that P-Rex1 has a phosphatase-like fold, the first of its type reported in the human genome (nearest ortholog is from Legionella!). Importantly, we identify the binding site of Gβγ, a downstream signaling component of GPCRs, on P-Rex1 to be in a completely unexpected location.