A Cdk1 phosphomimic mutant of MCAK impairs microtubule end recognition.
A Cdk1 phosphomimic mutant of MCAK impairs microtubule end recognition.
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作者：
Belsham HR;Friel CT
微管解聚驱动蛋白13（MCAK）在残基T537处被Cdk1磷酸化。这是MCAK运动域中唯一已知的磷酸化位点。为了了解Cdk1磷酸化对微管解聚活性的影响，我们研究了拟磷酸化突变体T537E的分子机制。该突变体显著损害微管解聚活性，并且当转染到细胞中时引起中期停滞和染色体错位。我们表明，这种磷酸模拟突变体的解聚活性降低的分子机制是无法识别微管末端。微管末端停留时间相对于野生型MCAK减少，而晶格停留时间不受拟磷酸化突变的影响。此外，微管末端特异性刺激ADP解离，MCAK的特征，被这种突变废除。我们的数据表明，T537 E不能区分微管末端和微管晶格。
The microtubule depolymerising kinesin-13, MCAK, is phosphorylated at residue T537 by Cdk1. This is the only known phosphorylation site within MCAK’s motor domain. To understand the impact of phosphorylation by Cdk1 on microtubule depolymerisation activity, we have investigated the molecular mechanism of the phosphomimic mutant T537E. This mutant significantly impairs microtubule depolymerisation activity and when transfected into cells causes metaphase arrest and misaligned chromosomes. We show that the molecular mechanism underlying the reduced depolymerisation activity of this phosphomimic mutant is an inability to recognise the microtubule end. The microtubule-end residence time is reduced relative to wild-type MCAK, whereas the lattice residence time is unchanged by the phosphomimic mutation. Further, the microtubule-end specific stimulation of ADP dissociation, characteristic of MCAK, is abolished by this mutation. Our data shows that T537E is unable to distinguish between the microtubule end and the microtubule lattice.
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