PMID- 32077153
OWN - NLM
STAT- MEDLINE
DCOM- 20210223
LR  - 20210602
IS  - 1469-896X (Electronic)
IS  - 0961-8368 (Print)
IS  - 0961-8368 (Linking)
VI  - 29
IP  - 6
DP  - 2020 Jun
TI  - Insights into allosteric control of microtubule dynamics from a buried beta-tubulin 
      mutation that causes faster growth and slower shrinkage.
PG  - 1429-1439
LID - 10.1002/pro.3842 [doi]
AB  - alphabeta-tubulin subunits cycle through a series of different conformations in the 
      polymer lattice during microtubule growing and shrinking. How these allosteric 
      responses to different tubulin:tubulin contacts contribute to microtubule 
      dynamics, and whether the contributions are evolutionarily conserved, remains 
      poorly understood. Here, we sought to determine whether the 
      microtubule-stabilizing effects (slower shrinking) of the beta:T238A mutation we 
      previously observed using yeast alphabeta-tubulin would generalize to mammalian 
      microtubules. Using recombinant human microtubules as a model, we found that the 
      mutation caused slow microtubule shrinking, indicating that this effect of the 
      mutation is indeed conserved. However, unlike in yeast, beta:T238A human 
      microtubules grew faster than wild-type and the mutation did not appear to 
      attenuate the conformational change associated with guanosine 5'-triphosphate 
      (GTP) hydrolysis in the lattice. We conclude that the assembly-dependent 
      conformational change in alphabeta-tubulin can contribute to determine the rates of 
      microtubule growing as well as shrinking. Our results also suggest that an 
      allosteric perturbation like the beta:T238A mutation can alter the behavior of 
      terminal subunits without accompanying changes in the conformation of fully 
      surrounded subunits in the body of the microtubule.
CI  - (c) 2020 The Protein Society.
FAU - Ye, Xuecheng
AU  - Ye X
AD  - UT Southwestern Medical Center, Departments of Biophysics and Biochemistry, 
      Dallas, Texas, USA.
FAU - Kim, Tae
AU  - Kim T
AD  - UT Southwestern Medical Center, Departments of Biophysics and Biochemistry, 
      Dallas, Texas, USA.
FAU - Geyer, Elisabeth A
AU  - Geyer EA
AD  - UT Southwestern Medical Center, Departments of Biophysics and Biochemistry, 
      Dallas, Texas, USA.
FAU - Rice, Luke M
AU  - Rice LM
AUID- ORCID: 0000-0001-6551-3307
AD  - UT Southwestern Medical Center, Departments of Biophysics and Biochemistry, 
      Dallas, Texas, USA.
LA  - eng
GR  - T32 GM008297/GM/NIGMS NIH HHS/United States
GR  - T32-GM008297/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200309
PL  - United States
TA  - Protein Sci
JT  - Protein science : a publication of the Protein Society
JID - 9211750
RN  - 0 (Protein Subunits)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tubulin)
SB  - IM
MH  - Allosteric Regulation
MH  - Humans
MH  - Microtubules/chemistry/*metabolism
MH  - Models, Molecular
MH  - *Mutation
MH  - Protein Subunits/chemistry/genetics/metabolism
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Tubulin/chemistry/*genetics/metabolism
PMC - PMC7255507
EDAT- 2020/02/23 06:00
MHDA- 2021/02/24 06:00
PMCR- 2021/06/01
CRDT- 2020/02/21 06:00
PHST- 2019/11/21 00:00 [received]
PHST- 2020/02/14 00:00 [revised]
PHST- 2020/02/17 00:00 [accepted]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2021/02/24 06:00 [medline]
PHST- 2020/02/21 06:00 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - PRO3842 [pii]
AID - 10.1002/pro.3842 [doi]
PST - ppublish
SO  - Protein Sci. 2020 Jun;29(6):1429-1439. doi: 10.1002/pro.3842. Epub 2020 Mar 9.