PMID- 28820593
OWN - NLM
STAT- MEDLINE
DCOM- 20180521
LR  - 20200317
IS  - 1520-5207 (Electronic)
IS  - 1520-5207 (Linking)
VI  - 121
IP  - 36
DP  - 2017 Sep 14
TI  - Structure of Dynamic, Taxol-Stabilized, and GMPPCP-Stabilized Microtubule.
PG  - 8427-8436
LID - 10.1021/acs.jpcb.7b01057 [doi]
AB  - Microtubule (MT) is made of alphabeta-tubulin heterodimers that dynamically assemble 
      into a hollow nanotube composed of straight protofilaments. MT dynamics is 
      facilitated by hydrolysis of guanosine-5'-triphosphate (GTP) and can be inhibited 
      by either anticancer agents like taxol or the nonhydrolyzable GTP analogues like 
      GMPPCP. Using high-resolution synchrotron X-ray scattering, we have measured and 
      analyzed the scattering curves from solutions of dynamic MT (in other words, in 
      the presence of excess GTP and free of dynamic-inhibiting agents) and examined 
      the effect of two MT stabilizers: taxol and GMPPCP. Previously, we have analyzed 
      the structure of dynamic MT by docking the atomic model of tubulin dimer onto a 
      3-start left handed helical lattice, derived from the PDB ID 3J6F . 3J6F 
      corresponds to a MT with 14 protofilaments. In this paper, we took into account 
      the possibility of having MT structures containing between 12 and 15 
      protofilaments. MTs with 12 protofilaments were never observed. We determined the 
      radii, the pitch, and the distribution of protofilament number that best fit the 
      scattering data from dynamic MT or stabilized MT by taxol or GMPPCP. We found 
      that the protofilament number distribution shifted when the MT was stabilized. 
      Taxol increased the mass fraction of MT with 13 protofilaments and decreased the 
      mass fraction of MT with 14 protofilaments. GMPPCP reduced the mass fraction of 
      MT with 15 protofilaments and increased the mass fraction of MT with 14 
      protofilaments. The pitch, however, remained unchanged regardless of whether the 
      MT was dynamic or stabilized. Higher tubulin concentrations increased the 
      fraction of dynamic MT with 14 protofilaments.
FAU - Ginsburg, Avi
AU  - Ginsburg A
AD  - Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem, 9190401, 
      Israel.
AD  - Institute for Drug Research, School of Pharmacy, The Hebrew University of 
      Jerusalem , Jerusalem, 9112102, Israel.
AD  - Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , 
      Jerusalem, 9190401, Israel.
FAU - Shemesh, Asaf
AU  - Shemesh A
AD  - Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem, 9190401, 
      Israel.
AD  - Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , 
      Jerusalem, 9190401, Israel.
FAU - Millgram, Abigail
AU  - Millgram A
AD  - Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem, 9190401, 
      Israel.
AD  - Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , 
      Jerusalem, 9190401, Israel.
FAU - Dharan, Raviv
AU  - Dharan R
AD  - Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem, 9190401, 
      Israel.
AD  - Azrieli College of Engineering , Jerusalem, 9103501, Israel.
FAU - Levi-Kalisman, Yael
AU  - Levi-Kalisman Y
AD  - Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , 
      Jerusalem, 9190401, Israel.
AD  - Institute of Life Sciences, The Hebrew University of Jerusalem , Jerusalem, 
      9190401, Israel.
FAU - Ringel, Israel
AU  - Ringel I
AD  - Institute for Drug Research, School of Pharmacy, The Hebrew University of 
      Jerusalem , Jerusalem, 9112102, Israel.
AD  - Azrieli College of Engineering , Jerusalem, 9103501, Israel.
FAU - Raviv, Uri
AU  - Raviv U
AUID- ORCID: 0000-0001-5992-9437
AD  - Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem, 9190401, 
      Israel.
AD  - Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , 
      Jerusalem, 9190401, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170901
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (Tubulin)
RN  - 4E15I11U9B (5'-guanylylmethylenebisphosphonate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Guanosine Triphosphate/*analogs & derivatives/chemistry
MH  - Microscopy, Electron, Transmission
MH  - Microtubules/*chemistry
MH  - Molecular Docking Simulation
MH  - Paclitaxel/*chemistry
MH  - Protein Stability
MH  - Protein Structure, Quaternary
MH  - Scattering, Radiation
MH  - Tubulin/*chemistry
MH  - X-Rays
EDAT- 2017/08/19 06:00
MHDA- 2018/05/22 06:00
CRDT- 2017/08/19 06:00
PHST- 2017/08/19 06:00 [pubmed]
PHST- 2018/05/22 06:00 [medline]
PHST- 2017/08/19 06:00 [entrez]
AID - 10.1021/acs.jpcb.7b01057 [doi]
PST - ppublish
SO  - J Phys Chem B. 2017 Sep 14;121(36):8427-8436. doi: 10.1021/acs.jpcb.7b01057. Epub 
      2017 Sep 1.