Noriyuki KODERA
Nano Life Science Institute (WPI – NanoLSI),
Kanazawa University

Single-molecule visualization of intrinsically disordered
Rett syndrome protein,
MeCP2 by high-speed Atomic Force Microscopy

Contact : nkodera [at sign] staff.kanazawa-u.ac.jp
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Noriyuki KODERA
Nano Life Science Institute (WPI – NanoLSI), Kanazawa University

Research Interestsbiophysics, molecular motors, cytoskeletons, atomic force microscopy

High-speed atomic force microscopy (HS-AFM) directly visualizes biological molecules in action at nanometerspatial and sub-second temporal resolution. The unique performance of HS-AFM has been demonstrated by direct
observations of many protein systems [1]. Importantly, HS-AFM can even resolve thin and flexible features of
intrinsically disordered regions (IDRs), single polypeptide chains with height of ~0.5 nm, in a protein that could notEducation
2001. Mar
2003. Mar2005. Sep

be analyzed by any techniques at single molecule level. In some cases, dynamic structural transitions in IDRs
B. Sci., Dept. of Phys, Fac. of Sci., Kanazawa Univ.

between ordered- and disordered-conformations can be directly visualized [2-4].
Here, we applied HS-AFM to Methyl-CpG binding protein 2 (MeCP2). MeCP2 is a chromatin regulatory protein

M. Sci., Div. of Math. & Phys. Sci., Grad. Sch. Nat. Sci. & Tech., Kanazawa Univ.

essential for brain development and activity in vertebrates. Specific missense and nonsense mutations in MeCP2Ph.D., Div. of Basic Sci., Grad. Sch. Nat. Sci. & Tech., Kanazawa Univ.

lead to the neurodevelopmental disorder, Rett syndrome (RTT). HS-AFM demonstrated that MeCP2 transitions
between a fully extended dumbbell-likestructure with the methyl DNA binding domain

Professional Career(MBD) and C-ter minal domain (CTD) at the2005 - 2010

Research Fellow (DC2 & PD), JSPS and Postdoctoral Fellow, CREST, JST

MBD and CTD interact in cis. The MBD within

Assistant Professor & Associate Professor, Bio-AFM Frontier Research Center, Institute of

the full length protein equilibrates between

Science and Engineering, Kanazawa University

unfolded and well folded states. MBD−CTD

2010 - 20182013 - 20172018 - present

PRESTO Researcher, JST
Professor, WPI-NanoLSI, Kanazawa University

extremities, and a compact structure where theinteractions stabilize the MBD in its folded state
and are essential for MeCP2 plasticity (Fig. 1).
The R106W, R133C, F155S and T158M R TT
mutations all showed aberrant MBD dynamics

Scientific Activities
2000 - 2008
2008 - present

Development of high-speed atomic force microscopy (HS-AFM)
Biological application studies using HS-AFM and improvement of HS-AFM

compared to wild type. Further more, weobserved sliding movements of MeCP2 along
dsDNA, bridging two adjacent dsDNAs andDNA condensations by MeCp2. These results
would gain insight into the molecular basis of
RTT [5].

MBD in its folded state.

Honors2017

JSPS Prize

2013

Prize for Science and Technology (Development Category), The Commendation for Science and2012

Young Researcher’s Nanoprobe Technology Prize (JSPS Nanoprobe Technology 167)

Technology by the Minister of Education, Culture, Sports, Science and Technology

Publications
1.

Kodera N, Noshiro D, Dora SK, …, Longhi S, Ando T, “Structural and dynamics analysis of intrinsically disordered proteins by high-speed atomic force
microscopy”, Nat. Nanotech. (in press).

2.

Ngo KX, Kodera N, Katayama E, Ando T, Uyeda TQ, “Cofilin-induced unidirectional cooperative conformational changes in actin filaments revealedby high-speed atomic force microscopy”, eLife 4, 04806 (2015).
Kodera N, Yamamoto D, Ishikawa R, Ando T, “Video imaging of walking myosin V by high-speed atomic force microscopy”, Nature 468, 72-76

3. (2010).
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Fig.1 HS-AFM images and schematics showing that MBD-CTD interactions stabilize theReferences[ 1 ] T. Ando, Curr. Opin. Chem. Biol., 2019, 51, 105-112.
[ 2 ] M. Hashimoto, N. Kodera, Y. Tsunaka, M. Oda, M. Tanimoto, T. Ando, K. Morikawa, and S. Tate, Biophys. J., 2013,
104, 2222-2234.
[ 3 ] N. Terahara, N. Kodera, T. Uchihashi, T. Ando, K. Namba, and T Minamino, Sci. Adv., 2017, 3, eaao4119.
[ 4 ] N. Kodera, D. Noshiro, SK. Dora, …, S. Longhi, and T. Ando, Nat. Nanotech. (in press).
[ 5 ] N. Kodera, AA. Kalashnikova, …, T. Ando, and JC. Hansen, (in revision).

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