Design principles of a microtubule polymerase

Elisabeth A. Geyer, Matthew P. Miller, Chad A Brautigam, Sue Biggins, Luke M Rice

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We show that polymerase activity does not require different kinds of TOGs, nor are there strict requirements for how the TOGs are linked. We identify an unexpected antagonism between the tubulin-binding TOGs and the lattice-binding basic region: lattice binding by the basic region is weak when at least two TOGs engage tubulins, strong when TOGs are empty. End-localization of Stu2 requires unpolymerized tubulin, at least two TOGs, and polymerase competence. We propose a ‘ratcheting’ model for processivity: transfer of tubulin from TOGs to the lattice activates the basic region, retaining the polymerase at the end for subsequent rounds of tubulin binding and incorporation. These results clarify design principles of the polymerase.

Original languageEnglish (US)
Article numbere34574
JournaleLife
Volume7
DOIs
StatePublished - Jun 13 2018

Fingerprint

Tubulin
Microtubules
Mental Competency
Elongation
Organizations
Chemical analysis
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Design principles of a microtubule polymerase. / Geyer, Elisabeth A.; Miller, Matthew P.; Brautigam, Chad A; Biggins, Sue; Rice, Luke M.

In: eLife, Vol. 7, e34574, 13.06.2018.

Research output: Contribution to journalArticle

Geyer, Elisabeth A. ; Miller, Matthew P. ; Brautigam, Chad A ; Biggins, Sue ; Rice, Luke M. / Design principles of a microtubule polymerase. In: eLife. 2018 ; Vol. 7.
@article{56d00d21fd9a4026aa931ef017348e37,
title = "Design principles of a microtubule polymerase",
abstract = "Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We show that polymerase activity does not require different kinds of TOGs, nor are there strict requirements for how the TOGs are linked. We identify an unexpected antagonism between the tubulin-binding TOGs and the lattice-binding basic region: lattice binding by the basic region is weak when at least two TOGs engage tubulins, strong when TOGs are empty. End-localization of Stu2 requires unpolymerized tubulin, at least two TOGs, and polymerase competence. We propose a ‘ratcheting’ model for processivity: transfer of tubulin from TOGs to the lattice activates the basic region, retaining the polymerase at the end for subsequent rounds of tubulin binding and incorporation. These results clarify design principles of the polymerase.",
author = "Geyer, {Elisabeth A.} and Miller, {Matthew P.} and Brautigam, {Chad A} and Sue Biggins and Rice, {Luke M}",
year = "2018",
month = "6",
day = "13",
doi = "10.7554/eLife.34574",
language = "English (US)",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Design principles of a microtubule polymerase

AU - Geyer, Elisabeth A.

AU - Miller, Matthew P.

AU - Brautigam, Chad A

AU - Biggins, Sue

AU - Rice, Luke M

PY - 2018/6/13

Y1 - 2018/6/13

N2 - Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We show that polymerase activity does not require different kinds of TOGs, nor are there strict requirements for how the TOGs are linked. We identify an unexpected antagonism between the tubulin-binding TOGs and the lattice-binding basic region: lattice binding by the basic region is weak when at least two TOGs engage tubulins, strong when TOGs are empty. End-localization of Stu2 requires unpolymerized tubulin, at least two TOGs, and polymerase competence. We propose a ‘ratcheting’ model for processivity: transfer of tubulin from TOGs to the lattice activates the basic region, retaining the polymerase at the end for subsequent rounds of tubulin binding and incorporation. These results clarify design principles of the polymerase.

AB - Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We show that polymerase activity does not require different kinds of TOGs, nor are there strict requirements for how the TOGs are linked. We identify an unexpected antagonism between the tubulin-binding TOGs and the lattice-binding basic region: lattice binding by the basic region is weak when at least two TOGs engage tubulins, strong when TOGs are empty. End-localization of Stu2 requires unpolymerized tubulin, at least two TOGs, and polymerase competence. We propose a ‘ratcheting’ model for processivity: transfer of tubulin from TOGs to the lattice activates the basic region, retaining the polymerase at the end for subsequent rounds of tubulin binding and incorporation. These results clarify design principles of the polymerase.

UR - http://www.scopus.com/inward/record.url?scp=85051946426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051946426&partnerID=8YFLogxK

U2 - 10.7554/eLife.34574

DO - 10.7554/eLife.34574

M3 - Article

C2 - 29897335

AN - SCOPUS:85051946426

VL - 7

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e34574

ER -