Decoupling of nucleotide- and microtubule-binding sites in a kinesin mutant

Nature ◽  
10.1038/25153 ◽  
1998 ◽  
Vol 396 (6711) ◽  
pp. 587-590 ◽  
Author(s):  
Hebok Song ◽  
Sharyn A. Endow
Keyword(s):  
Binding Sites ◽  
Microtubule Binding

Microtubule-binding sites of the CH domain of EB1 and its autoinhibition revealed by NMR

2013 ◽  
Vol 1834 (2) ◽  
pp. 499-507 ◽  
Author(s):  
Teppei Kanaba ◽  
Ryoko Maesaki ◽  
Tomoyuki Mori ◽  
Yutaka Ito ◽  
Toshio Hakoshima ◽  
...  
Keyword(s):  
Binding Sites ◽  
Microtubule Binding

scholarly journals Kinesin-4 Motor Teams Effectively Navigate Dendritic Microtubule Arrays Through Track Switching and Regulation of Microtubule Dynamics

2021 ◽  
Author(s):  
Erin M. Masucci ◽  
Peter K. Relich ◽  
Melike Lakadamyali ◽  
E. Michael Ostap ◽  
Erika L. F. Holzbaur
Keyword(s):  
Binding Sites ◽  
Intracellular Transport ◽  
Microtubule Dynamics ◽  
Directional Bias ◽  
Microtubule Binding ◽  
Directed Transport ◽  
Binding Regions ◽  
Mixed Polarity ◽  
Directional Transport

Microtubules establish the directionality of intracellular transport by kinesins and dynein through their polarized assembly, but it remains unclear how directed transport occurs along microtubules organized with mixed polarity. We investigated the ability of the plus-end directed kinesin-4 motor KIF21B to navigate mixed polarity microtubules in mammalian dendrites. Reconstitution assays with recombinant KIF21B and engineered microtubule bundles or extracted neuronal cytoskeletons indicate that nucleotide-independent microtubule binding regions of KIF21B modulate microtubule dynamics and promote directional switching on antiparallel microtubules. Optogenetic recruitment of KIF21B to organelles in live neurons resulted in unidirectional transport in axons but bi-directional transport with a net retrograde bias in dendrites; microtubule dynamics and the secondary microtubule binding regions are required for this net directional bias. We propose a model in which cargo-bound KIF21B motors coordinate nucleotide-sensitive and insensitive microtubule binding sites to achieve net retrograde movement along the dynamic mixed polarity microtubule arrays of dendrites.

scholarly journals Polyphosphate initiates tau aggregation through intra- and intermolecular scaffolding

2019 ◽  
Author(s):  
S. P. Wickramasinghe ◽  
J. Lempart ◽  
H. E. Merens ◽  
J. Murphy ◽  
U. Jakob ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Binding Sites ◽  
Cross Linking ◽  
Conformational Ensemble ◽  
Intensive Study ◽  
Rich Region ◽  
Microtubule Binding ◽  
Long Range Interactions ◽  
Tau Aggregation ◽  
Proline Rich Region

AbstractThe aggregation and deposition of tau is a hallmark of a class of neurodegenerative diseases called tauopathies. Despite intensive study, cellular and molecular factors that trigger tau aggregation are not well understood. Here we provide evidence for two mechanisms relevant to the initiation of tau aggregation in the presence of cytoplasmic polyphosphates (polyP): changes in the conformational ensemble of monomer tau and noncovalent cross-linking of multiple tau monomers. We identified conformational changes throughout full-length tau, most notably diminishment of long-range interactions between the termini coupled with compaction of the microtubule binding and proline rich regions. We found that while the proline rich and microtubule binding regions both contain polyP binding sites, the proline rich region is a requisite for compaction of the microtubule binding region upon binding. Additionally, both the magnitude of the conformational change and the aggregation of tau are dependent on the chain length of the polyP polymer. Longer polyP chains are more effective at intermolecular, noncovalent cross-linking of tau. These observations provide an understanding of the initial steps of tau aggregation through interaction with a physiologically relevant aggregation inducer.

Microtubule-associated protein 8 contains two microtubule binding sites

2006 ◽  
Vol 339 (1) ◽  
pp. 172-179 ◽  
Author(s):  
Jianqing Ding ◽  
Angela Valle ◽  
Elizabeth Allen ◽  
Wei Wang ◽  
Timothy Nardine ◽  
...  
Keyword(s):  
Binding Sites ◽  
Microtubule Binding

scholarly journals Hsp90–Sgt1 and Skp1 target human Mis12 complexes to ensure efficient formation of kinetochore–microtubule binding sites

2010 ◽  
Vol 189 (2) ◽  
pp. 261-274 ◽  
Author(s):  
Alexander E. Davies ◽  
Kenneth B. Kaplan
Keyword(s):  
Binding Sites ◽  
Protein Complexes ◽  
Large Fraction ◽  
Multiprotein Complex ◽  
Complex Assembly ◽  
Microtubule Binding ◽  
Kinetochore Assembly ◽  
Chromosome Alignment ◽  
Chaperone Complex

The formation of functional kinetochores requires the accurate assembly of a large number of protein complexes. The Hsp90–Sgt1 chaperone complex is important for this process; however, its targets are not conserved and its exact contribution to kinetochore assembly is unclear. Here, we show that human Hsp90–Sgt1 interacts with the Mis12 complex, a so-called keystone complex required to assemble a large fraction of the kinetochore. Inhibition of Hsp90 or Sgt1 destabilizes the Mis12 complex and delays proper chromosome alignment due to inefficient formation of microtubule-binding sites. Interestingly, coinhibition of Sgt1 and the SCF subunit, Skp1, increases Mis12 complexes at kinetochores and restores timely chromosome alignment but forms less-robust microtubule-binding sites. We propose that a balance of Mis12 complex assembly and turnover is required for the efficient and accurate assembly of kinetochore–microtubule binding sites. These findings support a novel role for Hsp90–Sgt1 chaperones in ensuring the fidelity of multiprotein complex assembly.

Dephosphorylation of Microtubule-Binding Sites at the Neurofilament-H Tail Domain by Alkaline, Acid, and Protein Phosphatases1

1993 ◽  
Vol 113 (6) ◽  
pp. 705-709 ◽  
Author(s):  
Shin-ichi Hisanaga ◽  
Setsuko Yasugawa ◽  
Takashi Yamakawa ◽  
Eishichi Miyamoto ◽  
Mitsuo Ikebe ◽  
...  
Keyword(s):  
Binding Sites ◽  
Tail Domain ◽  
Microtubule Binding

Microtubules pull the strings: disordered sequences as efficient couplers of microtubule-generated force

2020 ◽  
Vol 64 (2) ◽  
pp. 371-382
Author(s):  
Vladimir A. Volkov
Keyword(s):  
Binding Sites ◽  
Protein Complexes ◽  
Mechanical Tension ◽  
Microtubule Binding ◽  
Binding Domains ◽  
Force Coupling ◽  
Couple Dynamics ◽  
Systematic Understanding ◽  
Positively Charged ◽  
Cellular Organelles

Abstract Microtubules are dynamic polymers that grow and shrink through addition or loss of tubulin subunits at their ends. Microtubule ends generate mechanical force that moves chromosomes and cellular organelles, and provides mechanical tension. Recent literature describes a number of proteins and protein complexes that couple dynamics of microtubule ends to movements of their cellular cargoes. These ‘couplers’ are quite diverse in their microtubule-binding domains (MTBDs), while sharing similarity in function, but a systematic understanding of the principles underlying their activity is missing. Here, I review various types of microtubule couplers, focusing on their essential activities: ability to follow microtubule ends and capture microtubule-generated force. Most of the couplers require presence of unstructured positively charged sequences and multivalency in their microtubule-binding sites to efficiently convert the microtubule-generated force into useful connection to a cargo. An overview of the microtubule features supporting end-tracking and force-coupling, and the experimental methods to assess force-coupling properties is also provided.

Tension on chromosomes increases the number of kinetochore microtubules but only within limits

2000 ◽  
Vol 113 (21) ◽  
pp. 3815-3823 ◽  
Author(s):  
J.M. King ◽  
R.B. Nicklas
Keyword(s):  
Mitotic Spindle ◽  
Binding Sites ◽  
Turnover Rate ◽  
Direct Evidence ◽  
Tension Force ◽  
Limited Effect ◽  
Microtubule Binding ◽  
Original Number

When chromosomes attach properly to a mitotic spindle, their kinetochores generate force in opposite directions, creating tension. Tension is presumed to increase kinetochore microtubule number, but there has been no direct evidence this is true. We micromanipulated grasshopper spermatocyte chromosomes to test this assumption and found that tension does indeed affect the number of kinetochore microtubules. Releasing tension at kinetochores causes a drop to less than half the original number of kinetochore microtubules. Restoring tension onto these depleted kinetochores restores the microtubules to their original number. However, the effects of tension are limited. Prometaphase kinetochores, when under normal tension from mitotic forces, have about half as many microtubules as they will in late metaphase. We imposed a tension force of 6 × 10(−5) dynes, three times the normal tension, on prometaphase kinetochores. The elevated tension did not drive kinetochore microtubule number above normal prometaphase values. Tension probably increases the number of kinetochore microtubules by slowing their turnover rate. The limited effect of tension at prometaphase kinetochores suggests that they have fewer microtubule binding sites than at late metaphase. The relatively few sites available in prometaphase may be the decisive sites whose binding of microtubules regulates the dynamics of transient kinetochore constituents, including checkpoint components.

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