The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends

Andrew W. Hunter; Michael Caplow; David L. Coy; William O. Hancock; Stefan Diez; Linda Wordeman; Jonathon Howard

doi:10.1016/S1097-2765(03)00049-2

The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends

Andrew W. Hunter, Michael Caplow, David L. Coy, William O. Hancock, Stefan Diez, Linda Wordeman, Jonathon Howard

Research output: Contribution to journal › Article › peer-review

303 Scopus citations

Abstract

MCAK belongs to the Kin I subfamily of kinesin-related proteins, a unique group of motor proteins that are not motile but instead destabilize microtubules. We show that MCAK is an ATPase that catalytically depolymerizes microtubules by accelerating, 100-fold, the rate of dissociation of tubulin from microtubule ends. MCAK has one high-affinity binding site per protofilament end, which, when occupied, has both the depolymerase and ATPase activities. MCAK targets protofilament ends very rapidly (on-rate 54 μM^-1·s^-1), perhaps by diffusion along the microtubule lattice, and, once there, removes ∼20 tubulin dimers at a rate of 1 s^-1. We propose that up to 14 MCAK dimers assemble at the end of a microtubule to form an ATP-hydrolyzing complex that processively depolymerizes the microtubule.

Original language	English (US)
Pages (from-to)	445-457
Number of pages	13
Journal	Molecular cell
Volume	11
Issue number	2
DOIs	https://doi.org/10.1016/S1097-2765(03)00049-2
State	Published - Feb 1 2003

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

Access to Document

10.1016/S1097-2765(03)00049-2

Cite this

@article{5836381c1b1a4c9fbdf9d1dfd0ccca48,

title = "The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends",

abstract = "MCAK belongs to the Kin I subfamily of kinesin-related proteins, a unique group of motor proteins that are not motile but instead destabilize microtubules. We show that MCAK is an ATPase that catalytically depolymerizes microtubules by accelerating, 100-fold, the rate of dissociation of tubulin from microtubule ends. MCAK has one high-affinity binding site per protofilament end, which, when occupied, has both the depolymerase and ATPase activities. MCAK targets protofilament ends very rapidly (on-rate 54 μM-1·s-1), perhaps by diffusion along the microtubule lattice, and, once there, removes ∼20 tubulin dimers at a rate of 1 s-1. We propose that up to 14 MCAK dimers assemble at the end of a microtubule to form an ATP-hydrolyzing complex that processively depolymerizes the microtubule.",

author = "Hunter, {Andrew W.} and Michael Caplow and Coy, {David L.} and Hancock, {William O.} and Stefan Diez and Linda Wordeman and Jonathon Howard",

note = "Funding Information: We thank Mr. T. Sapra and Drs. A. Desai, A. Hyman, M. Landolfa, and E. Sch{\"a}ffer for comments on an earlier version of this manuscript. Mr. Sapra assisted with the motility assays. GMP-CPP was kindly provided by Drs. A. Desai and L. Amos. This work was supported by grants to A.W.H. (NIH, T326M07270), M.C. (NIH, GM59231), L.W. (NIH, GM53654A), and J.H. (NIH, AR40593; HFSP; and the Max Planck Society). ",

year = "2003",

month = feb,

day = "1",

doi = "10.1016/S1097-2765(03)00049-2",

language = "English (US)",

volume = "11",

pages = "445--457",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends

AU - Hunter, Andrew W.

AU - Caplow, Michael

AU - Coy, David L.

AU - Hancock, William O.

AU - Diez, Stefan

AU - Wordeman, Linda

AU - Howard, Jonathon

N1 - Funding Information: We thank Mr. T. Sapra and Drs. A. Desai, A. Hyman, M. Landolfa, and E. Schäffer for comments on an earlier version of this manuscript. Mr. Sapra assisted with the motility assays. GMP-CPP was kindly provided by Drs. A. Desai and L. Amos. This work was supported by grants to A.W.H. (NIH, T326M07270), M.C. (NIH, GM59231), L.W. (NIH, GM53654A), and J.H. (NIH, AR40593; HFSP; and the Max Planck Society).

PY - 2003/2/1

Y1 - 2003/2/1

N2 - MCAK belongs to the Kin I subfamily of kinesin-related proteins, a unique group of motor proteins that are not motile but instead destabilize microtubules. We show that MCAK is an ATPase that catalytically depolymerizes microtubules by accelerating, 100-fold, the rate of dissociation of tubulin from microtubule ends. MCAK has one high-affinity binding site per protofilament end, which, when occupied, has both the depolymerase and ATPase activities. MCAK targets protofilament ends very rapidly (on-rate 54 μM-1·s-1), perhaps by diffusion along the microtubule lattice, and, once there, removes ∼20 tubulin dimers at a rate of 1 s-1. We propose that up to 14 MCAK dimers assemble at the end of a microtubule to form an ATP-hydrolyzing complex that processively depolymerizes the microtubule.

AB - MCAK belongs to the Kin I subfamily of kinesin-related proteins, a unique group of motor proteins that are not motile but instead destabilize microtubules. We show that MCAK is an ATPase that catalytically depolymerizes microtubules by accelerating, 100-fold, the rate of dissociation of tubulin from microtubule ends. MCAK has one high-affinity binding site per protofilament end, which, when occupied, has both the depolymerase and ATPase activities. MCAK targets protofilament ends very rapidly (on-rate 54 μM-1·s-1), perhaps by diffusion along the microtubule lattice, and, once there, removes ∼20 tubulin dimers at a rate of 1 s-1. We propose that up to 14 MCAK dimers assemble at the end of a microtubule to form an ATP-hydrolyzing complex that processively depolymerizes the microtubule.

UR - http://www.scopus.com/inward/record.url?scp=0037292454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037292454&partnerID=8YFLogxK

U2 - 10.1016/S1097-2765(03)00049-2

DO - 10.1016/S1097-2765(03)00049-2

M3 - Article

C2 - 12620232

AN - SCOPUS:0037292454

SN - 1097-2765

VL - 11

SP - 445

EP - 457

JO - Molecular cell

JF - Molecular cell

IS - 2

ER -

The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this