Snapshots of actin and tubulin folding inside the TRiC chaperonin

The integrity of a cell's proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC. Tagging of the endogenous type II chaperonin TRiC complex using CRISPR knock-in enables its purification for cryo-EM. A series of structures reveal the fate of substrates and co-chaperones inside the TRiC chamber to uncover its inner workings.Peer reviewe

Autonomous and Lagrangian ocean observations for Atlantic tropical cyclone studies and forecasts

Author Posting. © The Oceanography Society, 2017. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 30, no. 2 (2017): 92–103, doi:10.5670/oceanog.2017.227.The tropical Atlantic basin is one of seven global regions where tropical cyclones (TCs) commonly originate, intensify, and affect highly populated coastal areas. Under appropriate atmospheric conditions, TC intensification can be linked to upper-ocean properties. Errors in Atlantic TC intensification forecasts have not been significantly reduced during the last 25 years. The combined use of in situ and satellite observations, particularly of temperature and salinity ahead of TCs, has the potential to improve the representation of the ocean, more accurately initialize hurricane intensity forecast models, and identify areas where TCs may intensify. However, a sustained in situ ocean observing system in the tropical North Atlantic Ocean and Caribbean Sea dedicated to measuring subsurface temperature, salinity, and density fields in support of TC intensity studies and forecasts has yet to be designed and implemented. Autonomous and Lagrangian platforms and sensors offer cost-effective opportunities to accomplish this objective. Here, we highlight recent efforts to use autonomous platforms and sensors, including surface drifters, profiling floats, underwater gliders, and dropsondes, to better understand air-sea processes during high-wind events, particularly those geared toward improving hurricane intensity forecasts. Real-time data availability is key for assimilation into numerical weather forecast models.The NOAA/AOML component of this work was originally funded by the Disaster Relief Appropriations Act of 2013, also known as the Sandy Supplemental, and is currently funded through NOAA research grant NA14OAR4830103 by AOML and CARICOOS, as well as NOAA’s Integrated Ocean Observing System (IOOS). The TEMPESTS component of this work is supported by NOAA through the Cooperative Institute for the North Atlantic Region (NA13OAR4830233) with additional analysis support from the WHOI Summer Student Fellowship Program, Nortek Student Equipment Grant, and the Rutgers University Teledyne Webb Graduate Student Fellowship Program. The drifter component of this work is funded through NOAA grant NA15OAR4320071(11.432) in support of the Global Drifter Program