Retrospect and Prospect of Single Particle Cryo-Electron Microscopy: The Class of Integral Membrane Proteins as an Example.

Abstract:

:A giant technological leap in the field of cryo-electron microscopy (cryo-EM) has assured the achievement of near-atomic resolution structures of biological macromolecules. As a recognition of this accomplishment, the Nobel Prize in Chemistry was awarded in 2017 to Jacques Dubochet, Joachim Frank, and Richard Henderson, the pioneers in the field of cryo-EM. Currently, the technique has become the method of choice for structural analysis of heterogeneous and intrinsically dynamic biological complexes. In the past few years, the most prolific branch of cryo-EM, single particle analysis, has revolutionized the structural biology field and structural investigation of membrane proteins, in particular. To achieve high-resolution structures of macromolecules in noncrystalline specimens, from sample and grid preparation to image acquisition, image data processing, and analysis of 3D maps, methodological advances in each of the steps play critical roles. In this Review, we discuss two areas in single particle cryo-EM, the remarkable developments in sample preparation strategies, particularly for membrane proteins, and breakthroughs in methodologies for molecular model building on the high-resolution 3D density maps that brought promises to resolve high-resolution (<4 Å) structures of biological macromolecules.

journal_name

J Chem Inf Model

authors

Akbar S,Mozumder S,Sengupta J

doi

10.1021/acs.jcim.9b01015

subject

Has Abstract

pub_date

2020-05-26 00:00:00

pages

2448-2457

issue

5

eissn

1549-9596

issn

1549-960X

journal_volume

60

pub_type

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