Highly Ordered Self-Assembly of Native Proteins into 1D, 2D, and 3D Structures Modulated by the Tether Length of Assembly-Inducing Ligands

Article abstract of DOI:10.1002/anie.201703052

In nature, proteins self-assemble into various structures with different dimensions. To construct these nanostructures in laboratories, normally proteins with different symmetries are selected. However, most of these approaches are engineering-intensive and highly dependent on the accuracy of the protein design. Herein, we report that a simple native protein LecA assembles into one-dimensional nanoribbons and nanowires, two-dimensional nanosheets, and three-dimensional layered structures controlled mainly by small-molecule assembly-inducing ligands RnG (n=1, 2, 3, 4, 5) with varying numbers of ethylene oxide repeating units. To understand the formation mechanism of the different morphologies controlled by the small-molecule structure, molecular simulations were performed from microscopic and mesoscopic view, which presented a clear relationship between the molecular structure of the ligands and the assembled patterns. These results introduce an easy strategy to control the assembly structure and dimension, which could shed light on controlled protein assembly.

Full text of DOI:10.1002/anie.201703052

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Highly ordered self-assembly of native proteins into 1D, 2D and
3D structures modulated by a tether length of inducing ligands
Authors: Guang Yang, Hong-ming Ding, Zdravko Kochovski, Rongting
Hu, Yan Lu, Yu-qiang Ma, Guosong Chen, and Ming Jiang
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201703052
Angew. Chem. 10.1002/ange.201703052
Link to VoR: http://dx.doi.org/10.1002/anie.201703052
http://dx.doi.org/10.1002/ange.201703052

10.1002/anie.201703052
Angewandte Chemie International Edition
Highly ordered self-assembly of native proteins into 1D, 2D and
3D structures modulated by a tether length of inducing ligands
Guang Yanga‡, Hong-ming Dingb‡, Zdravko Kochovskic‡, Rongting Hua, Yan Luc,e, Yu-qiang Mab,d*,
Guosong Chena*, Ming Jianga
building block always leads to only one morphology. In very
few elegant designs, metal-ligand interaction has been
employed to achieve different assembled structures, [14, 16] but
engineered protein building blocks still could not be avoided.
Apparently, there is an exceptional challenge to achieve
morphologies with different dimensions from one natural
protein by slightly tuning the assembly conditions.
Abstract: Proteins self-assemble into various structures with
different dimensions in nature. To construct these nanostructures in
laboratories, normally proteins with different symmetries are
selected.
However,
most
of
these
approaches
are
engineering-intensive and highly dependent on the accuracy of the
protein design. In this paper, we report that a simple native protein
LecA assembles into one dimensional nanoribbon, nanowire, two
dimensional nanosheets as well as three dimensional layered
structures controlled mainly by small molecular inducing ligands RnG
(n=1, 2, 3, 4, 5) with varying number of ethylene oxide repeating
units. In order to understand the formation mechanism of the different
morphologies controlled by the small molecular structure, molecular
simulations were performed from microscopic and mesoscopic view,
which presented a clear relationship between the molecular structure
of the ligands and the assembled patterns. These results introduce
an easy strategy to control assembly structure and dimension, which
could shed light on controlled protein assembly in the near future.
Recently, we successfully prepared 3D crystalline
frameworks[13b] and 1D helical nanotube[10c] by combining the
molecular recognition between lectins and sugars and π−π
interactions.. However, in these two reports, concanavalin A
(Con A) and soybean agglutinin (SBA) with different shapes
were employed to construct the framework and nanotube,
separately. In this paper, we demonstrate that by using this
strategy, when native protein LecA with cuboid shape[17] is
employed as the building block, five kinds of protein assembly
structures were obtained by slightly tuning the molecular
structure of the inducing ligands and salt concentration.
Specifically, only by changing the number of ethylene oxide
repeating units from 1 to 5, 1D nanoribbons, nanowires, 2D
crystalline nanosheets and 3D layered structures were generated
from the same natural protein building block. It is noteworthy
that among these structures, the unsupported 2D protein
nanosheets with regular spatial arrangements and patterns were
the most interesting one,[18] which could not be easily achieved
in protein assembly.[19] Moreover, to demonstrate that the
significant morphology change of the assemblies was indeed
caused by the trivial structure change of the small molecular
ligands, all-atom molecular dynamic simulations were
employed and the connection between morphology of the
assemblies and chemical structure of ligands was revealed.
Proteins are remarkable building blocks for fabrication of
different functional materials due to their enormous structural
complexity and intrinsic functions.[1] In nature, proteins
self-assemble into different structures in nm or µm scale with
highly ordered patterns,[2] e.g. virus capsids, [3] actin filaments, [4]
microtubules,[5] bacteria S-layers[6] etc. These attractive
structures have stimulated strong motivation for programming
proteins into various nano-objects,[7] including oligomers8[a,b]
,
zero-dimensional (0D) nanocages,[8b,c] 1D fibers,[9] nanotubes,[10]
2D nanosheets, [11] nanorings[12] and 3D frameworks[13] etc.
However, most natural proteins could be treated as colloidal
particles without canonical interacting motifs for precise
organization. [2, 14] To achieve regular protein packing structures
in laboratory, intensively engineered proteins with
well-selected geometry and symmetry are always employed to
control protein-protein interactions (PPIs), which highly
depended on the accuracy of the protein designs.[15]
Unfortunately, in most cases, a single engineered protein
To achieve a range of morphologies from the same protein,
a protein with multiple packing patterns is required. LecA (PA-
IL) from Pseudomonas aeruginosa, which is a homotetrameric
aThe State Key Laboratory of Molecular Engineering of Polymers,
Department of Macromolecular Science and Collaborative Innovation
Center of Genetics and Development, Fudan University, Shanghai 200433,
China
bCenter for Soft Condensed Matter Physics and Interdisciplinary Research,
Soochow University, Suzhou 215006, China
cSoft Matter and Functional Materials, Helmholtz-Zentrum Berlin für
Materialien und Energie, 14109 Berlin, Germany
dNational Laboratory of Solid State Microstructures and Department of
Physics, Collaborative Innovation Center of Advanced Microstructures,
Nanjing University, Nanjing 210093, China
Figure 1. a) Structure of LecA tetramer from Protein Data Bank (PDB
code: 4LKD). b) Chemical structures of inducing ligands RnG (n = 1 to 5)
and R4M. c) Driving force of LecA/RnG assemblies. d) Three possible
packing patterns of LecA/RnG.
eInstitute of Chemistry, University of Potsdam, 14476 Potsdam, Germany
protein with a cuboid-shaped structure (length~7.2 nm, width
~3.5 nm and height ~1.9 nm) is selected as the building block
Corresponding Authors guosong@fudan.edu.cn (G.C.),
myqiang@nju.edu.cn (Y. M.)
‡These authors contribute equally to this work.
1
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10.1002/anie.201703052
Angewandte Chemie International Edition
for assembly fabrication (Figure 1a). LecA is galactose-specific
and plays an important role in infection process, especially in
biofilm formation.[20] According to our previous reports,[10c, 13b]
i.e. proteins are connected via the molecular recognition
between lectin and sugar and the π−π stacking of rhodamine B
(RhB) between the neighbouring ligands (Figure 1c), five
linkages, π−π stacking between the neighboring RhB was
observed (Figure 2e, f). Nevertheless, the diagonal-diagonal
linkage was found not stable enough i.e. it may change to
different conformations upon time (Figure S4), which made this
structure unfavorable for the subsequent packing of proteins.
On the contrary, LecA/R1G showed easier to pack via the
short-short linkage and form the protofilament (Figure 2e).
Moreover, the potentials of the mean forces (PMF) for the
short-short and diagonal-diagonal packing were calculated. As
shown in Figure S5, the energy well in short-short packing was
deeper than that of diagonal-diagonal, indicating that this
linkage in LecA/R1G assembly was energy-favorable. On the
basis of above discussion, we summarize that the short-short
packing is optimal for LecA/R1G assembly. Fortunately, the
results from experiment and simulation were consistent to each
other, which indicated that the simulation method was reliable
to explain the experimental results.
inducing ligands RnG (n
=
1
to 5) containing
Galactopyranoside (Gal) and RhB are prepared with different
tether length, i.e. the number of ethylene oxide repeating units
varies from 1 to 5 (Figure 1b).. A compound containing RhB
but with Mannopyranoside, which does not interact with LecA,
replacing Gal was also prepared as a control (R4M). Based on
the protein packing in crystal structure of LecA-sugar
complex,[21] in our design, three kinds of packing patterns
formed by LecA with different side length were possible, i.e.
short-short, long-long and diagonal-diagonal (Figure 1d).
The condition for LecA/RnG assembly was similar ([RnG]
= 0.1 mM, [LecA] = 0.05 mM (calculated as monomer) in
Tris-HCl (25 mM) buffer with [Ca2+] = 0.75 mM, pH 7.5, room
temperature).We started with R1G, the ligand with the shortest
linker. First the self-assembled structure of LecA/R1G formed
was observed. As shown in Figure 2a, 1D nanoribbon structure
was found by transmission electron microscopy (TEM) with
negative staining. Under Atomic Force Microscope (AFM), it
was quite obvious that the ribbons were formed by a layer of
protein protofilaments packing in parallel (Figure 2b). The
height of the ribbons was only about 2 nm, which was
consistent to the height of a LecA tetramer. The width of each
protofilament was just several nanometers, so AFM could not
give a precise diameter because of the curvature radius of AFM
tip.[22] Then by using negative stained TEM,
a single
protofilament was clearly observed with a diameter ~3.5 nm,
which is closed to the short width of LecA (Figure 2a inset,
Figure S1). Meanwhile, the results from cryo-TEM supported
the size of protofilaments and their packing into nanoribbon
(Figure S2). Combining the above results, the LecA/R1G
ribbon formation process was proposed in Figure 2c. R1G was
tethered to the surface of LecA due to the recognition between
LecA and Gal, then the RhB moiety on the surface of LecA
polymerized resulting the formation of protein protofilament by
short-short linkage. The protofilaments further assembled side
by side leading to the formation of 1D nanoribbons.
Figure 2. a) TEM micrograph with negative stained LecA/R1G assembly
(inset: protein protofilament found in some areas). b) AFM micrograph of
LecA/R1G assembly (inset: height measured along the black line). c) The
plausible mechanism of LecA/R1G self-assembly. MD simulation result of
d) long-long, e) short-short, and f) diagonal-diagonal packing of
LecA/R1G, in which only the short-short one is possible for large-scale
assembly.
As we mentioned earlier that three different packing styles of
LecA/RnG are possible. Why did LecA/R1G prefer the
short-short linkage during the assembly? To answer this
question, all-atom molecular dynamics simulation was firstly
employed (Figure S3 and the detailed simulation method was in
supporting information). To simplify the simulation process,
Gal moiety of R1G was first placed on the sugar binding sites
of LecA and each of the binding sites of one tetramer LecA was
made to be occupied. This manipulation was reasonable as in
our previous reports, we proved that the binding of sugars to
proteins took place before the dimerization of RhB.[13b] Then a
couple of LecA/R1G complexes (LecA as a tetramer) were
initially placed closely, in long-long, diagonal-diagonal and
short-short linkages separately (Figure S3b-d). Since the tether
length of R1G is very short, the π−π stacking between the RhB
moieties on neighbouring LecA/R1G complexes could be
restricted. As a result, long-long linkage would be excluded
(Figure 2d), because the neighbouring RhB moieties were far
from each other. While for short-short and diagonal-diagonal
Similarly, the self-assembled structure of LecA/R2G was
observed by cryo-TEM. The results were shown in Figure 3a
presenting
a clear lattice structure, among which the
representative ones marked in the white box were in the size of
about 30 nm × 50 nm. In the enlarged photograph (inset image
of Figure 3a), the lattice pattern clearly showed that the proteins
were connected by the diagonal-diagonal linkage. AFM
measurement also revealed that the height of these protein
patterns being only about 2 nm (Figure 3b, c), which was
consistent to the height of a tetramer LecA, revealing that the
nanosheets were made by only one layer of LecA proteins. And
for LecA/R4G and LecA R5G, the same kind of assemblies as
LecA/R2G was found (Figure 3d-g, Figure S6 and S7). In brief,
LecA/RnG (n = 2, 4, 5) assembled into 2D nanosheets in a
diagonal-diagonal style (Figure 3h). These nanosheets were
dispersed in solution unsupported, i.e. free-standing, which was
proved by the data from DLS (Figure S8). Synchrotron
small-angle X-ray scattering (SAXS) was utilized to further
2
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10.1002/anie.201703052
Angewandte Chemie International Edition
verify the ordered structure of the 2D LecA/R4G assemblies in
solution (Figure S9), showing an obvious peak corresponding
to the d-space center at about 5 nm, which was consistent to the
spacing observed from cryo-TEM (Figure 3e). Furthermore, the
π−π stacking between RhB was supported by UV-vis and
circular dichroism (CD) spectra (Figure S10a, c, d). DLS and
CD (Figure S10b, c) also proved that formation of these 2D
lattices was driven by the molecular recognition between
LecA/Gal and π−π stacking of RhB. This was proved by the
control ligand R4M and the dissociation of the assembly after
adding the competitive molecules of either free Gal or
β-cyclodextrin (β-CD) into the solution. In addition, the
isoelectric point (pI) of LecA is about 4.9,[20] which indicates
that at pH =7.5, LecA exists with negative net charge in
aqueous solution. So when the NaCl (from 100 to 400 mM)
was added into LecA/R4G solution with respect to ion strength,
it was found that the 2D nano-sheets stacked into the 3D arrays
due to the reduced electrostatic repulsion between different
layers (Figure S11 and S12).
To understand why the diagonal-diagonal packing
dominates in the cases of LecA/RnG (n=2, 4, 5), MD
simulation was employed as well. Two LecA/R2G complexes
were first placed closely via long-long linkages. However, even
if they were pushed close, stable structure could not be formed
(Figure S13a), since the π−π stacking between the neighboring
RhB did not take place, which was very similar to the result of
LecA/R1G. But when two LecA/R2Gs were put closely in the
short-short and diagonal-diagonal linkages, the π−π stacking
between small molecules on different LecA was quickly
formed (Figure S13b and Figure 3i). More importantly, here the
structure made by diagonal-diagonal linkage changed very little
with time (Figure S14), and was more stable compared to that
in the case of LecA/R1G (Figure S4), which is beneficial for
the subsequent packing. Besides, one should notice that
although the stable short-short linkage could also occur, our
Brownian dynamics (BD) simulations (Figure S15) showed that
the structure formed by the short-short linkage was much more
flexible than that based on the diagonal-diagonal one (Figure
S16). In the research field of supramolecular chemistry, it has
been known that relatively rigid linkers do promote the
elongation of supramolecular polymers.[23] Considering the
possible supramolecular polymeric structure of LecA/R2G, it is
predictable that the rigid diagonal-diagonal linkage results in
larger assemblies. While for R4G/R5G, in addition to the
short-short and diagonal-diagonal linkages, the long-long
linkage was also observed (Figure S17 and S18). However, the
possible assemblies of LecA/R4G or LecA/R5G based on the
long-long or short-short linkages were soft compared to those
formed in the diagonal-diagonal linkages (Figure S16b, c).
Similar to the case of R2G, the 2D lattice (i.e.
diagonal-diagonal linkage) finally won out probably because its
high rigidity helped its growth to larger assemblies in the cases
of LecA/R4G and LecA/R5G.
Figure 3. a) Cryo-TEM micrograph (inset: enlarged cryo-TEM micrograph
of the nanosheet and Fourier-transform image) and b) AFM image of 2D
LecA/R2G lattice. c) The height of LecA/R2G nanosheet along the black
line in b). d) Cryo-TEM (inset: Fourier-transform image) and e) enlarged
cryo-TEM micrographs of 2D LecA/R4G nanosheet. f) Cryo-TEM (inset:
Fourier-transform image) and g) enlarged cryo-TEM micrographs of 2D
LecA/R5G nanosheet. h) The plausible assemblied mechanism of
LecA/RnG (n= 2, 4, or 5) 2D nanosheet. i) MD simulation result of
diagonal-diagonal packing of LecA/R2G.
Very interestingly, the assembly of LecA/R3G presented a
unique morphology differing from the 1D nanoribbons and 2D
nanosheets mentioned above. First of all, DLS revealed that
self-assembly of LecA and R3G took place (Figure S19). TEM
with negative staining revealed that the morphology of
LecA/R3G assembly was 1D nanowire with a width about 21
nm (Figure 4a), which of course was far from a single protein
protofilament. In fact, at the end of the nanowire, several slim
protofilaments were observed (Figure 4b) with width about 9
nm, which was close to the long side width of LecA tetramer.
This observation indicated that the nanowires were made by
slim protofilaments (formed via length-length linkage) twisting
together. Cryo-TEM also supported the morphology of
3
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10.1002/anie.201703052
Angewandte Chemie International Edition
nanowire (Figure 4c, S20). Fortunately, in some areas, the
single protofilament can be observed clearly. Under cryo-TEM,
the width of the nanowire was about 19 nm while the width of
the protofilament was about 7.4 nm (Figure 4d), which is
consistent with the long size width of LecA. The diameters of
the nanowires and the protofilaments measured by cryo-TEM
were slightly smaller than those measured under negative
staining, which was reasonable due to the collapsed state of
materials under high vacuum. Based on these data, we proposed
that the nanowires were formed by several protein
protofilaments, while every protofilament was formed by LecA
in a long-long linkage (Figure 4e). In this case, MD simulations
were also used to reveal the possibility of three packing styles.
Different from the case of LecA/R1G and LecA/R2G due to
the long length of R3G, in addition to the short-short and
diagonal-diagonal linkage (Figure S21a and b), here the
long-long linkage can also occur (Figure S21c). In this sense,
the packing styles here are similar to the case of LecA/R4G and
LecA/R5G. However, since the tether length of R3G is shorter
compared to those of R4G and R5G, the rigidity of the
assembly of LecA/R3G with long-long linkage is close to that
of the corresponding assemblies of R4G and R5G (Figure S16),
which might be the reason for the nanowire in a long-long
linkage. However, when the concentration of NaCl was
increased to more than 100 mM, the packing style of
LecA/R3G became diagonal-diagonal and also formed 3D
layerd structures (Figure S22, S23).
In summary, we demonstrated that different morphologies
from 1D nanoribbon, nanowire, to 2D nanosheet and 3D
layered structure were easily achieved by LecA/RnG when the
linker length of the inducing ligand RnG was slightly changed.
In this cases, native protein LecA was used, no molecular
engineering on the protein was required. The success of this
assembly not only demonstrated the beauty of the dual
non-covalent interactions, i.e. lectin-sugar interaction and π−π
stacking in the field of protein self-assembly, but also showed
that accurate structural control of the inducing ligand did play
crucial roles in the assembly process. By controlling the salt
concentration, the electrostatic interaction between the
negatively charged proteins and the RhB groups with positive
charge might also contribute to the assembly process, which
deserves deep discussion in our future research. This simple
approach of building protein assemblies with different
dimensions will be useful to prepare various functional
materials with precise structure and well-controlled
morphology.
Figure 4. a-b) Negative stained TEM and c-d) cryo-TEM micrographs of
LecA/R3G assembly. e) Possible mechanism of LecA/R3G assembly.
Acknowledgements
We thank National Natural Science Foundation of China (No.
21504016, 91527305 and GZ962), National Center for Protein
Science Shanghai (Cryo-TEM) and Shanghai Synchrotron
Radiation Facility (synchrotron SAXS, and Joint Lab for
Structural Research at the Integrative Research Institute for the
Sciences ),
Keywords: Protein self-assembly •carbohydrate-protein
interaction • dual non-covalent interaction • molecular simulation
References:
[1] a) T. Ueno, Chem.–Eur. J. 2013, 19, 9096-9102; b) G. Yang, L. Wu, G.
Chen, M. Jiang, Chem. Commun. 2016, 52, 10595-10605.
[2] B. J. G. E. Pieters, M. B. Van Eldijk, R. J. M. Nolte, J. Mecinovic, Chem.
Soc. Rev. 2016, 45, 24-39.
[3] J. M. Alonso, M. Ł. Górzny, A. M. Bittner, Trends Biotechnol. 2013, 31,
530-538.
[4] A. Mogilner, G. Oster, Biophys. J. 1996, 71, 3030-3045.
[5] M. A. Jordan, L. Wilson, Nat. Rev. Cancer 2004, 4, 253-265.
[6] S. Scheuring, H. Stahlberg, M. Chami, C. Houssin, J. L. Rigaud, A. Engel,
Mol. Microbiol. 2002, 44, 675-684.
[7] a) E. N. Salgado, R. J. Radford, F. A. Tezcan, Acc. Chem. Res. 2010, 43,
661-672; b) Y. Bai, Q. Luo, J. Liu, Chem. Soc. Rev. 2016, 45, 2756-2767;
c) O. Koji, O. Akira, H. Takashi, Chem. Commun. 2012, 48,11714-11726;
d) T. O. Yeates, Y. Liu, J. Laniado, Curr. Opin. Struct. Biol. 2016, 39,
134-143.
[8] a) R. E. Mcgovern, A. A. Mccarthy, P. B. Crowley, Chem. Commun. 2014,
50, 10412-10415; b) M. L. Rennie, A. M. Doolan, C. L. Raston, P. B.
Crowley, Angew. Chem., Int. Ed. 2017, 56, 5517-5521; c) J. E. Padilla, C.
Colovos, T. O. Yeates, Proc. Natl. Acad. Sci. U. S.
A .2001, 98,
2217-2221; d) N. P. King, J. B. Bale, W. Sheffler, M. N. Dan, S. Gonen, T.
Gonen, T. O. Yeates, D. Baker, Nature 2014, 510, 103-108.
[9] a) C. Hou, J. Li, L. Zhao, W. Zhang, Q. Luo, Z. Dong, J. Xu, J. Liu, Angew.
Chem., Int. Ed. 2013, 52, 5590-5593; b) W. Zhang, Q. Luo, L. Miao, C.
Hou, Y. Bai, Z. Dong, J. Xu, J. Liu, Nanoscale 2012, 4, 5847-5851; c) H.
Kitagishi, K. Oohora, H. Yamaguchi, H. Sato, T. Matsuo, A. Harada, T.
Hayashi, J. Am. Chem. Soc. 2007, 129, 10326-10327.
4
This article is protected by copyright. All rights reserved.

10.1002/anie.201703052
Angewandte Chemie International Edition
[10] a) J. D. Brodin, S. J. Smith, J. R. Carr, F. A. Tezcan, J. Am. Chem. Soc.
2015, 137, 10468-10471; b) S. Biswas, K. Kinbara, N. Oya, N. Ishii, H.
Taguchi, T. Aida, J. Am. Chem. Soc. 2009, 131, 7556-7557; c) G. Yang, Z.
Xiang, Z. Kochovski, Y. Zhang, B. Dai, F. Sakai, J. Lin, L. Yan, M. Ballauff,
X. Li, C. Liu, G. Chen, M. Jiang, J. Am. Chem. Soc. 2016, 138, 1932-1937.
[11] a) Y. Suzuki, G. Cardone, D. Restrepo, P. D. Zavattieri, T. S. Baker, F. A.
Tezcan, Nature 2016, 533, 369-373; b) S. Gonen, F. Dimaio, T. Gonen, D.
Baker, Science 2015, 348, 1365-1368; c) Y. N. Kim, Y. Jung, Org. Biomol.
Chem. 2016, 14, 5352-5356; c) Sarah M. Dimick, Steven C. Powell,
Stephen A. McMahon, Davina N. Moothoo, James H. Naismith, Eric J.
Toone, J. Am. Chem. Soc. 2000, 121,10286-10296.
[12] a) T. F. Chou, C. So, B. R. White, J. C. Carlson, M. Sarikaya, C. R. Wagner,
ACS Nano 2008, 2, 2519-2525; b) Y. Bai, Q. Luo, W. Zhang, L. Miao, J. Xu,
H. Li, J. Liu, J. Am. Chem. Soc. 2013, 135, 10966-10969.
[13] a) P. A. Sontz, J. B. Bailey, S. Ahn, F. A. Tezcan, J. Am. Chem. Soc. 2015,
137, 11598-11601; b) F. Sakai, G. Yang, M. S. Weiss, Y. Liu, G. Chen, M.
Jiang, Nat. Commun. 2014, 5, 4634; c) Y. T. Lai, E. Reading, G. L. Hura,
K. L. Tsai, A. Laganowsky, F. J. Asturias, J. A. Tainer, C. V. Robinson, T.
O. Yeates, Nat. Chem. 2014, 6, 1065-1171; d) V. Liljeström, J. Mikkilä, M.
A. Kostiainen, Nat. Commun 2014, 5, 5445; e) M. Künzle, T. Eckert, T.
Beck, J. Am. Chem. Soc. 2016, 138, 12731-12734.
[14] J. D. Brodin, J. R. Carr, P. A. Sontz, F. A. Tezcan, Proc. Natl. Acad. Sci. U.
S. A. 2014, 111, 2897-2902.
[15] a) C. S. Zhang, L. H. Lai, Acta Phys.-Chim. Sin. 2012, 28, 2363-2380; b) J.
C. Sinclair, K. M. Davies, C. Vénienbryan, M. E. M. Noble, Nat.
nanotechnol. 2011, 6, 558-562.
[16] a) J. D. Brodin, X. I. Ambroggio, C. Tang, K. N. Parent, T. S. Baker, F. A.
Tezcan, Nat. Chem. 2012, 4, 375-382; b) S. P. Qiao, C. Lang, R. D. Wang,
X. M. Li, T. F. Yan, T. Z. Pan, L. L. Zhao, X. T. Fan, X. Zhang, C. X. Hou,
Nanoscale 2016, 8, 333-341.
[17] V. Wittmann, R. J. Pieters, Chem. Soc. Rev. 2013, 42, 4492-4503.
[18] S. Z. Butler, S. M. Hollen, L. Cao, Y. Cui, J. A. Gupta, H. R. Gutiérrez, T. F.
Heinz, S. S. Hong, J. Huang, A. F. Ismach, ACS Nano 2013, 7,
2898-2926.
[19]
Q.
Luo,
C.
Hou,
Y.
Bai,
R.
Wang,
J.
Liu, Chem. Rev. 2016, 116, 13571-13632.
[20] A. Imberty, M. Wimmerová, E. P. Mitchell, N. Gilboagarber, Microbes and
Infect. 2004, 6, 221-228.
[21] a) R. U. Kadam, M. Bergmann, D. Garg, G. Gabrieli, A. Stocker, T. Darbre,
J. L. Reymond,Chem.– Eur. J. 2013, 19, 17054-17063; b) A. Novoa, T.
Eierhoff, J. Topin, A. Varrot, S. Barluenga, A. Imberty, W. Römer, N.
Winssinger, Angew. Chem., Int. Ed. 2014, 53, 8885-8889.
[22] D. Sicard, S. Cecioni, M. Iazykov, Y. Chevolot, S. E. Matthews, J. P. Praly,
E. Souteyrand, A. Imberty, S. Vidal, M. Phanergoutorbe, Chem. Commun.
2011, 47, 9483-9485.
[23] J. F. Xu, L. Chen, X. Zhang, Chem.–Eur. J. 2015, 21, 11938-11946.
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10.1002/anie.201703052
Angewandte Chemie International Edition
COMMUNICATION
Guang Yanga‡, Hong-ming Dingb‡,
Zdravko Kochovskic‡, Rongting Hua,
Yan Luc,e, Yu-qiang Mab,d*, Guosong
Chena*, Ming Jianga
Highly ordered self-assembly of
native proteins into 1D, 2D and 3D
structures modulated by a tether
length of inducing ligands
6
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