Arron fenton biography definition

I received my Ph.D. in Biophysics from the Instituto Venezolano de Investigaciones Cientificas and my post-doctoral training at Harvard where I am now Professor of Cell Biology and Pediatrics, and Senior Investigator at Boston Children’s Hospital. I love science, nice people, windsurfing and dancin

Seeing is believing; visual observations are a vital part of scientific studies. They are also key to the communication of science to the public and the participation of the public in the importance of scientific research and we use them to transmit knowledge and interpretation

Our work has been characterized by use of emerging technologies — from the early days of molecular cloning to contemporary high-resolution structural visualization and live-cell imaging. We started with the tools of x-ray crystallography, cryo electron microscopy, and single-molecule biophysics to create a “molecular movie” of clathrin-mediated endocytosis, and in this way related these molecular events to functional properties of the surfaces of living cells.

Direct observation of molecular events in vivo is a key goal of contemporary microscopy. Two recently developed forms of fluorescence microscopy available in our laboratory — Lattice Light Sheet Microscopy (LLSM) and Lattice Light Sheet Microscopy optimized with Adaptive Optics (AO-LLSM) — are poised to bridge the gap between molecules and cells, either as independent entities in culture, as components of organoids, or as components of living tissues. The richness and magnitude of the data over periods ranging from seconds to hours, create new challenges for obtaining quantitative representations of the observed dynamics and for deriving accurate and comprehensive models for the underlying mechanism

Our current research program includes development of the new kinds of visualization and analysis software required by the scale and complexity of the datasets, and use of LLSM and

Published in final edited form as: Cell. 2023 Feb 9;186(5):1039–1049.e17. doi: 10.1016/j.cell.2023.01.013

SUMMARY

Hsp60 chaperonins and their Hsp10 cofactors assist protein folding in all living cells, constituting the paradigmatic example of molecular chaperones. Despite extensive investigations of their structure and mechanism, crucial questions regarding how these chaperonins promote folding remain unsolved. Here, we report that the bacterial Hsp60 chaperonin GroEL forms a stable, functionally relevant complex with the chaperedoxin CnoX, a protein combining a chaperone and a redox function. Binding of GroES (Hsp10 cofactor) to GroEL induces CnoX release. Cryo-electron microscopy provided crucial structural information on the GroEL-CnoX complex, showing that CnoX binds GroEL outside the substrate-binding site via a highly conserved C-terminal α-helix. Furthermore, we identified complexes in which CnoX, bound to GroEL, forms mixed disulfides with GroEL substrates, indicating that CnoX likely functions as a redox quality-control plugin for GroEL. Proteins sharing structural features with CnoX exist in eukaryotes, suggesting that Hsp60 molecular plugins have been conserved through evolution.

Keywords: Protein folding, chaperones, redox, proteostasis, TPR, thioredoxin, chaperonin

Graphical Abstract

In Brief:

CnoX is a redox quality-control molecular plugin for an evolutionarily conserved Hsp60 chaperonin complex crucial for protein folding in all living cells

INTRODUCTION

Following synthesis as linear amino-acid chains, proteins must fold to unique three-dimensional (3D) structures to become functional. Seminal work from Anfinsen demonstrated that the information required for a polypeptide to reach its native conformation is contained in its primary sequence. For most small proteins, folding to the native state is a spontaneous process that takes less than a few milliseconds. For larger protein