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TitleHuman β-Tubulin Isotypes Can Regulate Microtubule Protofilament Number and Stability.
Journal, issue, pagesDev Cell, Vol. 47, Issue 2, Page 175-190.e5, Year 2018
Publish dateOct 22, 2018
AuthorsShih-Chieh Ti / Gregory M Alushin / Tarun M Kapoor /
PubMed AbstractCell biological studies have shown that protofilament number, a fundamental feature of microtubules, can correlate with the expression of different tubulin isotypes. However, it is not known if ...Cell biological studies have shown that protofilament number, a fundamental feature of microtubules, can correlate with the expression of different tubulin isotypes. However, it is not known if tubulin isotypes directly control this basic microtubule property. Here, we report high-resolution cryo-EM reconstructions (3.5-3.65 Å) of purified human α1B/β3 and α1B/β2B microtubules and find that the β-tubulin isotype can determine protofilament number. Comparisons of atomic models of 13- and 14-protofilament microtubules reveal how tubulin subunit plasticity, manifested in "accordion-like" distributed structural changes, can accommodate distinct lattice organizations. Furthermore, compared to α1B/β3 microtubules, α1B/β2B filaments are more stable to passive disassembly and against depolymerization by MCAK or chTOG, microtubule-associated proteins with distinct mechanisms of action. Mixing tubulin isotypes in different proportions results in microtubules with protofilament numbers and stabilities intermediate to those of isotypically pure filaments. Together, our findings indicate that microtubule protofilament number and stability can be controlled through β-tubulin isotype composition.
External linksDev Cell / PubMed:30245156 / PubMed Central
MethodsEM (helical sym.)
Resolution3.5 - 3.65 Å
Structure data

8997

6e7b

EMDB-8997: 13-pf 3-start GMPCPP-human alpha1B/beta3 microtubules decorated with kinesin-1 motor domain
PDB-6e7b: 13-pf 3-start GMPCPP-human alpha1B/beta3 microtubules
Method: EM (helical sym.) / Resolution: 3.5 Å

8998

6e7c

EMDB-8998: 14-pf 3-start GMPCPP-human alpha1B/beta2B microtubules decorated with kinesin-1 motor domain
PDB-6e7c: 14-pf 3-start GMPCPP-human alpha1B/beta2B microtubules
Method: EM (helical sym.) / Resolution: 3.65 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-G2P:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-CPP, energy-carrying molecule analogue*YM

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / cytoskeleton / microtubules / recombinant human tubulin / tubulin isotype

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