Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition

Ren, Jinqi; Wang, Shuang; Chen, Han; Wang, Wenjuan; Huo, Linsheng; Feng, Wei

doi:10.1073/pnas.1811209115

Cited by 47 publications

(80 citation statements)

References 43 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, a cargo-induced monomer-to-dimer transition has been suggested to regulate members of both the kinesin and myosin superfamilies. For kinesin motors, cargoinduced dimerization was first suggested for the kinesin-3 family members murine KIF1A and its Caenorhabditis elegans homolog Unc-104 (12,(59)(60)(61) and has subsequently been demonstrated for additional members of the kinesin-3 family (17,(62)(63)(64)(65)(66)(67). For myosin motors, cargo-mediated dimerization has been demonstrated to regulate the motility of members of the myosin-6, myosin-7, and myosin-10 families (68-74).…”

Section: Peroxisome Dispersionmentioning

confidence: 99%

Intracellular cargo transport by single-headed kinesin motors

Schimert¹,

Budaitis²,

Reinemann³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Kinesin motor proteins that drive intracellular transport share an overall architecture of two motor domain-containing subunits that dimerize through a coiled-coil stalk. Dimerization allows kinesins to be processive motors, taking many steps along the microtubule track before detaching. However, whether dimerization is required for intracellular transport remains unknown. Here, we address this issue using a combination of in vitro and cellular assays to directly compare dimeric motors across the kinesin-1, -2, and -3 families to their minimal monomeric forms. Surprisingly, we find that monomeric motors are able to work in teams to drive peroxisome dispersion in cells. However, peroxisome transport requires minimal force output, and we find that most monomeric motors are unable to disperse the Golgi complex, a high-load cargo. Strikingly, monomeric versions of the kinesin-2 family motors KIF3A and KIF3B are able to drive Golgi dispersion in cells, and teams of monomeric KIF3B motors can generate over 8 pN of force in an optical trap. We find that intracellular transport and force output by monomeric motors, but not dimeric motors, are significantly decreased by the addition of longer and more flexible motor-to-cargo linkers. Together, these results suggest that dimerization of kinesin motors is not required for intracellular transport; however, it enables motor-to-motor coordination and high force generation regardless of motor-to-cargo distance. Dimerization of kinesin motors is thus critical for cellular events that require an ability to generate or withstand high forces.molecular motor | kinesin | microtubule | intracellular transport | monomeric motor

show abstract

Section: Peroxisome Dispersionmentioning

confidence: 99%

Intracellular cargo transport by single-headed kinesin motors

Schimert¹,

Budaitis²,

Reinemann³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In PNAS, Ren et al (22) finally solve this puzzle utilizing a combination of biochemistry and X-ray crystallography. The authors studied the mechanism of kinesin-3 self-regulated dimerization by determining structures of KIF13B self-folded monomeric and dimerized conformations (Fig.…”

mentioning

confidence: 99%

“…Deletion of CC1 led to spontaneous kinesin-3 dimerization and increased MTactivated ATP hydrolysis. Ren et al (22) present X-ray structures of the monomeric and dimeric kinesin-3, revealing the long-sought role of CC1 in the transition to dimerization. In the monomeric state, CC1 and NC α-helices form an antiparallel intramolecular coiled-coil assembly.…”

mentioning

confidence: 99%

“…1). Thus, CC1b forms the equivalent of a safety belt, further stabilizing the kinesin-3 monomeric CC1-NC folded state and inhibiting its disassembly (22).…”

mentioning

confidence: 99%

“…The thick and thin arrows describe an equilibrium and point in the direction of the more and less favorable states, respectively. Models were generated using Protein Data Bank ID codes described previously (22,23).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Malleable folding of coiled-coils regulates kinesin-3 dimerization

Al-Bassam

Nithianantham

2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Intracellular Cargo Transport by Single-Headed Kinesin Monomers

Schimert

Budaitis

Verhey

2017

Biophysical Journal

View full text Add to dashboard Cite

Cytoplasmic dynein-1 is a 1.4 MDa motor protein, which performs essential cargo transport to the minus end of microtubules. Long distance movement of single dynein-1 molecules is induced by binding to its 23-subunit cofactor dynactin and a cargo-adaptor protein. Here we present the cryo-EM structure of isolated human dynein-1 in its inhibited, phi-particle conformation. We achieved a resolution of 3.8Å for the motor domains and 8.4Å in the highly-flexible tail region. We reveal the architecture of the complete complex; identify all subunits, build helices in the tail and a full atomic model for the human dynein-1 motor domains. Mutagenesis to disrupt the interface between the two motor domains is not sufficient to activate dynein-1. Instead dynactin is required to orient the motors in a parallel fashion so that they can interact correctly with microtubules, thus explaining the structural mechanism of dynein-1 activation.

show abstract

Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition

Cited by 47 publications

References 43 publications

Intracellular cargo transport by single-headed kinesin motors

Intracellular cargo transport by single-headed kinesin motors

Malleable folding of coiled-coils regulates kinesin-3 dimerization

Intracellular Cargo Transport by Single-Headed Kinesin Monomers

Contact Info

Product

Resources

About