Thank you for attending THSNA 2026. The virtual meeting is now closed.
| Novel approaches to CryoEM of platelet surface proteins to characterize platelet disorders Xu Han. |
Abstract
Platelets play a critical role in physiological processes by sensing the extracellular environment through their membrane proteins. Changing the quantity or quality of these proteins can profoundly affect platelet physiology and impact health. The native membrane environment provides essential additional regulatory cues that impact the protein structure and mechanism of action.
Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins and large macromolecules to be solved from highly purified, homogeneous samples. Our recent breakthroughs in data processing make it feasible to obtain high-resolution protein structures from crude preparations in their native environments by integrating cryo-EM with the novel "Build and Retrieve" (BaR) data processing methodology. By performing in silico purification, image sorting, and model building from large heterogeneous datasets, this iterative bottom-up methodology has allowed us to solve the structures of several key platelet membrane proteins at a near-atomic resolution from samples extracted straight from human platelet membranes.
Currently, our pipeline that combines cryo-EM with the "Build and Retrieve" data processing method allows us to observe the natural modifications on macromolecules, elucidate the dynamic rearrangement of proteins, and reveal novel conformations from their native environment. Our data show the power of this method to uncover novel structures directly from natural sources, thereby identifying unrecognized regulatory mechanisms for proteins without artifacts introduced by purification processes. A distinct advantage of the BaR method is that it is an unbiased approach for solving multiple structures from raw samples, highlighting the potential of building a protein structural atlas from platelets. These data have the potential to enrich our understanding of platelet signaling circuitry and foster the development of higher-quality diagnoses and treatments for patients with platelet disorders.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.