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John C. H. Spence

Bio: John C. H. Spence is an academic researcher from Arizona State University. The author has contributed to research in topics: Diffraction & Electron diffraction. The author has an hindex of 69, co-authored 411 publications receiving 21361 citations. Previous affiliations of John C. H. Spence include Lawrence Berkeley National Laboratory & Arizona's Public Universities.


Papers
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Journal ArticleDOI
Henry N. Chapman1, Petra Fromme2, Anton Barty, Thomas A. White, Richard A. Kirian2, Andrew Aquila, Mark S. Hunter2, Joachim Schulz, Daniel P. DePonte, Uwe Weierstall2, R. Bruce Doak2, Filipe R. N. C. Maia3, Andrew V. Martin, Ilme Schlichting4, Lukas Lomb4, Nicola Coppola5, Robert L. Shoeman4, Sascha W. Epp4, Robert Hartmann, Daniel Rolles4, Artem Rudenko4, Lutz Foucar4, Nils Kimmel4, Georg Weidenspointner4, Peter Holl, Mengning Liang, Miriam Barthelmess, Carl Caleman, Sébastien Boutet6, Michael J. Bogan6, Jacek Krzywinski6, Christoph Bostedt6, Saša Bajt, Lars Gumprecht, Benedikt Rudek4, Benjamin Erk4, Carlo Schmidt4, André Hömke4, Christian Reich, Daniel Pietschner4, Lothar Strüder4, Günter Hauser4, H. Gorke7, Joachim Ullrich4, Sven Herrmann4, Gerhard Schaller4, Florian Schopper4, Heike Soltau, Kai-Uwe Kühnel4, Marc Messerschmidt6, John D. Bozek6, Stefan P. Hau-Riege8, Matthias Frank8, Christina Y. Hampton6, Raymond G. Sierra6, Dmitri Starodub6, Garth J. Williams6, Janos Hajdu3, Nicusor Timneanu3, M. Marvin Seibert3, M. Marvin Seibert6, Jakob Andreasson3, Andrea Rocker3, Olof Jönsson3, Martin Svenda3, Stephan Stern, Karol Nass1, Robert Andritschke4, Claus Dieter Schröter4, Faton Krasniqi4, Mario Bott4, Kevin Schmidt2, Xiaoyu Wang2, Ingo Grotjohann2, James M. Holton9, Thomas R. M. Barends4, Richard Neutze10, Stefano Marchesini9, Raimund Fromme2, Sebastian Schorb11, Daniela Rupp11, M. Adolph11, Tais Gorkhover11, Inger Andersson12, Helmut Hirsemann, Guillaume Potdevin, Heinz Graafsma, Björn Nilsson, John C. H. Spence2 
03 Feb 2011-Nature
TL;DR: This work offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage, by using pulses briefer than the timescale of most damage processes.
Abstract: X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded(1-3). It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source(4). We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes(5). More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (similar to 200 nm to 2 mm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes(6). This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.

1,708 citations

Journal ArticleDOI
M. Marvin Seibert1, Tomas Ekeberg1, Filipe R. N. C. Maia1, Martin Svenda1, Jakob Andreasson1, Olof Jönsson1, Dusko Odic1, Bianca Iwan1, Andrea Rocker1, Daniel Westphal1, Max F. Hantke1, Daniel P. DePonte, Anton Barty, Joachim Schulz, Lars Gumprecht, Nicola Coppola, Andrew Aquila, Mengning Liang, Thomas A. White, Andrew V. Martin, Carl Caleman1, Stephan Stern2, Chantal Abergel3, Virginie Seltzer3, Jean-Michel Claverie3, Christoph Bostedt4, John D. Bozek4, Sébastien Boutet4, A. Miahnahri4, Marc Messerschmidt4, Jacek Krzywinski4, Garth J. Williams4, Keith O. Hodgson4, Michael J. Bogan4, Christina Y. Hampton4, Raymond G. Sierra4, D. Starodub4, Inger Andersson5, Sǎa Bajt, Miriam Barthelmess, John C. H. Spence6, Petra Fromme6, Uwe Weierstall6, Richard A. Kirian6, Mark S. Hunter6, R. Bruce Doak6, Stefano Marchesini7, Stefan P. Hau-Riege8, Matthias Frank8, Robert L. Shoeman9, Lukas Lomb9, Sascha W. Epp9, Robert Hartmann, Daniel Rolles9, Artem Rudenko9, Carlo Schmidt9, Lutz Foucar9, Nils Kimmel9, Peter Holl, Benedikt Rudek9, Benjamin Erk9, André Hömke9, Christian Reich, Daniel Pietschner9, Georg Weidenspointner9, Lothar Strüder9, Günter Hauser9, H. Gorke, Joachim Ullrich9, Ilme Schlichting9, Sven Herrmann9, Gerhard Schaller9, Florian Schopper9, Heike Soltau, Kai Uwe Kuhnel9, Robert Andritschke9, Claus Dieter Schröter9, Faton Krasniqi9, Mario Bott9, Sebastian Schorb10, Daniela Rupp10, M. Adolph10, Tais Gorkhover10, Helmut Hirsemann, Guillaume Potdevin, Heinz Graafsma, Björn Nilsson, Henry N. Chapman2, Janos Hajdu1 
03 Feb 2011-Nature
TL;DR: This work shows that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source.
Abstract: The start-up of the Linac Coherent Light Source (LCLS), the new femtosecond hard X-ray laser facility in Stanford, California, has brought high expectations of a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. Two papers in this issue of Nature present proof-of-concept experiments showing the LCLS in action. Chapman et al. tackle structure determination from nanocrystals of macromolecules that cannot be grown in large crystals. They obtain more than three million diffraction patterns from a stream of nanocrystals of the membrane protein photosystem I, and assemble a three-dimensional data set for this protein. Seibert et al. obtain images of a non-crystalline biological sample, mimivirus, by injecting a beam of cooled mimivirus particles into the X-ray beam. The start-up of the new femtosecond hard X-ray laser facility in Stanford, the Linac Coherent Light Source, has brought high expectations for a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. This new capability is tested for the problem of imaging a non-crystalline biological sample. Images of mimivirus are obtained, the largest known virus with a total diameter of about 0.75 micrometres, by injecting a beam of cooled mimivirus particles into the X-ray beam. The measurements indicate no damage during imaging and prove the concept of this imaging technique. X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions1,2,3,4. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma1. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval2. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source5. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.

838 citations

Journal ArticleDOI
TL;DR: In this article, an inversion method was used to reconstruct the image of the object without the need for any such prior knowledge, without the knowledge of the shape of the objects and the low spatial frequencies unavoidably lost in experiments.
Abstract: A solution to the inversion problem of scattering would offer aberration-free diffraction-limited three-dimensional images without the resolution and depth-of-field limitations of lens-based tomographic systems. Powerful algorithms are increasingly being used to act as lenses to form such images. Current image reconstruction methods, however, require the knowledge of the shape of the object and the low spatial frequencies unavoidably lost in experiments. Diffractive imaging has thus previously been used to increase the resolution of images obtained by other means. Here we experimentally demonstrate an inversion method, which reconstructs the image of the object without the need for any such prior knowledge.

787 citations

Journal ArticleDOI
20 Jul 2012-Science
TL;DR: Serial femtosecond crystallography (SFX) is applied using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals of the well-characterized model protein lysozyme, demonstrating the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.
Abstract: Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.

764 citations

Journal ArticleDOI
30 Jul 2015-Nature
TL;DR: The crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin is determined by serial femtosecond X-ray laser crystallography and provides a basis for understanding GPCR-mediated arrestin-biased signalling.
Abstract: G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a similar to 20 degrees rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.

672 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
01 Apr 1988-Nature
TL;DR: In this paper, a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) is presented.
Abstract: Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

9,929 citations

Journal ArticleDOI
10 Mar 1970

8,159 citations

Journal ArticleDOI
18 Nov 2005-Science
TL;DR: Covalent organic frameworks (COFs) have been designed and successfully synthesized by condensation reactions of phenyl diboronic acid and hexahydroxytriphenylene to form rigid porous architectures with pore sizes ranging from 7 to 27 angstroms.
Abstract: Covalent organic frameworks (COFs) have been designed and successfully synthesized by condensation reactions of phenyl diboronic acid {C6H4[B(OH)2]2} and hexahydroxytriphenylene [C18H6(OH)6]. Powder x-ray diffraction studies of the highly crystalline products (C3H2BO)6.(C9H12)1 (COF-1) and C9H4BO2 (COF-5) revealed expanded porous graphitic layers that are either staggered (COF-1, P6(3)/mmc) or eclipsed (COF-5, P6/mmm). Their crystal structures are entirely held by strong bonds between B, C, and O atoms to form rigid porous architectures with pore sizes ranging from 7 to 27 angstroms. COF-1 and COF-5 exhibit high thermal stability (to temperatures up to 500 degrees to 600 degrees C), permanent porosity, and high surface areas (711 and 1590 square meters per gram, respectively).

4,843 citations

Journal ArticleDOI
01 Mar 2007-Nature
TL;DR: These studies by transmission electron microscopy reveal that individual graphene sheets freely suspended on a microfabricated scaffold in vacuum or air are not perfectly flat: they exhibit intrinsic microscopic roughening such that the surface normal varies by several degrees and out-of-plane deformations reach 1 nm.
Abstract: Graphene — a recently isolated one-atom-thick layered form of graphite — is a hot topic in the materials science and condensed matter physics communities, where it is proving to be a popular model system for investigation. An experiment involving individual graphene sheets suspended over a microscale scaffold has allowed structure determination using transmission electron microscopy and diffraction, perhaps paving the way towards an answer to the question of why graphene can exist at all. The 'two-dimensional' sheets, it seems, are not flat, but wavy. The undulations are less pronounced in a two-layer system, and disappear in multilayer samples. Learning more about this 'waviness' may reveal what makes these extremely thin carbon membranes so stable. Investigations of individual graphene sheets freely suspended on a microfabricated scaffold in vacuum or in air reveal that the membranes are not perfectly flat, but exhibit an intrinsic waviness, such that the surface normal varies by several degrees, and out-of-plane deformations reach 1 nm. The recent discovery of graphene has sparked much interest, thus far focused on the peculiar electronic structure of this material, in which charge carriers mimic massless relativistic particles1,2,3. However, the physical structure of graphene—a single layer of carbon atoms densely packed in a honeycomb crystal lattice—is also puzzling. On the one hand, graphene appears to be a strictly two-dimensional material, exhibiting such a high crystal quality that electrons can travel submicrometre distances without scattering. On the other hand, perfect two-dimensional crystals cannot exist in the free state, according to both theory and experiment4,5,6,7,8,9. This incompatibility can be avoided by arguing that all the graphene structures studied so far were an integral part of larger three-dimensional structures, either supported by a bulk substrate or embedded in a three-dimensional matrix1,2,3,9,10,11,12. Here we report on individual graphene sheets freely suspended on a microfabricated scaffold in vacuum or air. These membranes are only one atom thick, yet they still display long-range crystalline order. However, our studies by transmission electron microscopy also reveal that these suspended graphene sheets are not perfectly flat: they exhibit intrinsic microscopic roughening such that the surface normal varies by several degrees and out-of-plane deformations reach 1 nm. The atomically thin single-crystal membranes offer ample scope for fundamental research and new technologies, whereas the observed corrugations in the third dimension may provide subtle reasons for the stability of two-dimensional crystals13,14,15.

4,653 citations