Micro Electron Diffraction of Toxic and/or Infectious Macromolecular Nanoassemblies
Micro Electron Diffraction of Toxic and/or Infectious Macromolecular Nanoassemblies
批准号:
10458543
负责人:
Jose Alfonso Rodriguez
金额:
$37.16万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-08-01 至 2024-07-31
关键词:
3-DimensionalAmyloidosisBiologyBreathingCoupledCryoelectron MicroscopyCrystallizationCrystallographyDevelopmentDiagnosticDiseaseElectron MicroscopyElectronsGoalsKnowledgeLifeMacromolecular ComplexesMethodsMicro Electron DiffractionMindModernizationMolecular StructureProcessResolutionScienceStructureSystemTechniquesTherapeuticVisible RadiationX-Ray Crystallographyexperimental studyinstrumentinstrumentationmacromolecular assemblymacromoleculenanoassemblynanoscalenovelprotein structurestructural biologytool
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Despite modern advances in structural biology, structures of many biomedically relevant
macromolecular assemblies remain out of reach or lack atomic resolution detail. In addition, the
process of determining entirely novel structures remains laborious. Large crystals required for
conventional crystallography experiments are a challenge to grow, and determination of
structures from small or imperfect crystals by x-ray crystallography remains limited. Cryo-
electron microscopy (cryo-EM) methods promise to bring new life to high-throughput
approaches in macromolecular structure determination. The cryo-EM revolution has brought
with it new high-resolution methods including micro electron diffraction (MicroED). MicroED
exploits the strong interaction between electrons and nano-scale three-dimensional crystals by
leveraging emerging cryo-EM instrumentation against established crystallographic knowledge.
My group has helped achieve milestone discoveries in MicroED and determined entirely new
protein structures from crystals and crystal fragments smaller than the wavelength of visible
light, at atomic resolution. These technological advances, coupled with the greater availability of
advanced cryoEM instruments, present an opportunity for further improvement of high-
throughput structure determination. The development new and more efficient approaches to
structure determination by MicroED could open new avenues for comprehensive exploration of
complex macromolecular structures that remain out of reach for standard methods. These
systems include macromolecular complexes that grow small, fragile, or imperfect crystals. The
biomedical problems associated with these types of assemblies are varied and could broadly
impact biomedicine, both through the basic interpretation of disease and as therapeutic
platforms. Specifically, we aim to target infectious and/or toxic filamentous nanoassemblies
associated with amyloid disease. Through our efforts in determining these challenging
structures, we find inspiration to guide the improvement and development of cryoEM
techniques, particularly MicroED. With this goal in mind, my group will take on the development
of new high-throughput methods for crystallographic structure determination while obtaining
structures of pressing biomedical targets at truly atomic resolution.
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Structures from the Mesophase: MicroED Targets Crystals Extracted from LCP.
中间相结构:MicroED 目标是从 LCP 中提取的晶体。
DOI:
10.1016/j.str.2020.09.005
发表时间:
2020
期刊:
Structure (London, England : 1993)
影响因子:
--
作者:
[Gallagher-Jones,Marcus, Rodriguez,JoseA]
通讯作者:
Rodriguez,JoseA
DOI:
10.1021/acs.chemrev.1c00879
发表时间:
2022-09-14
期刊:
CHEMICAL REVIEWS
影响因子:
62.1
作者:
[Saha, Ambarneil, Nia, Shervin S., Rodriguez, Jose A.]
通讯作者:
Rodriguez, Jose A.
DOI:
10.12688/f1000research.25097.1
发表时间:
2020-01-01
期刊:
F1000Research
影响因子:
--
作者:
[Thompson, Michael C, Yeates, Todd O, Rodriguez, Jose A]
通讯作者:
Rodriguez, Jose A
DOI:
10.1038/s41594-017-0018-0
发表时间:
2018-03
期刊:
Nature structural & molecular biology
影响因子:
16.8
作者:
[Gallagher-Jones M, Glynn C, Boyer DR, Martynowycz MW, Hernandez E, Miao J, Zee CT, Novikova IV, Goldschmidt L, McFarlane HT, Helguera GF, Evans JE, Sawaya MR, Cascio D, Eisenberg DS, Gonen T, Rodriguez JA]
通讯作者:
Rodriguez JA
DOI:
10.1007/978-1-0716-0966-8_17
发表时间:
2021
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
作者:
[Zee CT, Saha A, Sawaya MR, Rodriguez JA]
通讯作者:
Rodriguez JA
Micro Electron Diffraction of Toxic and/or Infectious Macromolecular Nanoassemblies
-
批准号:10219307
-
项目类别:
-
资助金额:$37.16万
-
财政年份:2018
-
负责人:Jose Alfonso Rodriguez
-
依托单位:
海外基金