Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends DOI Open Access
Lauren A McCormick, Joseph M. Cleary, William O. Hancock

и другие.

Опубликована: Июль 21, 2023

Abstract GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding ‘poisoning’ plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

Higher-order protein assembly controls kinetochore formation DOI
Gunter B. Sissoko, Ekaterina V. Tarasovetc, Océane Marescal

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(1), С. 45 - 56

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

9
Elucidating the Molecular Landscape of Cystic Kidney Disease: Old Friends, New Friends and Some Surprises DOI Creative Commons
Deborah Watson, Frank Mentch,

Jonathan Billings

и другие.

American Journal of Medical Genetics Part A, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

ABSTRACT Cystic kidney diseases (CyKD) are a diverse group of disorders affecting more than 1 in 1000 individuals. Over 120 genes implicated, primarily encoding components the primary cilium, transcription factors, and morphogens. Prognosis varies greatly by molecular diagnosis. Causal variants not identified 10%–60% individuals due to our limited understanding CyKD. To elucidate landscape CyKD, we queried CAG Biobank using ICD10 codes N28.1, Q61.1, Q61.11, Q61.19, Q61.2, Q61.3, Q61.8 identify with One hundred eight met clinical criteria for CyKD underwent proband‐only exome sequencing. were 86/108 (80%) The most common diagnoses PKD1 ‐related autosomal dominant polycystic disease (32/108; 30%) recessive (21/108; 19%). Other ciliopathy syndromes (7/108; 6.5%) Tuberous Sclerosis (6/108; 5.6%). Seven had previously associated 6.5%). Candidate five (5/108; 4.5%). Discordance between diagnosis was present two We demonstrate high rate that can result diagnostic reclassification, supporting role genetic testing

Язык: Английский

Процитировано

0
Recent Advances in DNA‐Templated Protein Patterning DOI Open Access

Qinglin Xia,

Mo Zhou, Kai Jiao

и другие.

Small Methods, Год журнала: 2025, Номер unknown

Опубликована: Фев. 2, 2025

Abstract In recent decades, the advancement of DNA nanotechnology enables precise nanoscale organization diverse functional materials with templates. Particularly, a variety DNA‐templated protein patterns are constructed as powerful tools for programming biomimetic complexes. this review, progress in patterning, including cutting‐edge methods arranging proteins templates, and across varying dimensions briefly summarized. Representative applications biological analysis biomedicine discussed. DNA‐protein programmable dynamics, which hold promise precision diagnosis therapeutics highlighted. Finally, current challenges opportunities fabrication application pattering

Язык: Английский

Процитировано

0
CLASPs stabilize the pre-catastrophe intermediate state between microtubule growth and shrinkage DOI Creative Commons
Elizabeth J. Lawrence, Saptarshi Chatterjee, Marija Žanić

и другие.

The Journal of Cell Biology, Год журнала: 2023, Номер 222(7)

Опубликована: Май 15, 2023

Cytoplasmic linker-associated proteins (CLASPs) regulate microtubules in fundamental cellular processes. CLASPs stabilize dynamic by suppressing microtubule catastrophe and promoting rescue, the switch-like transitions between growth shrinkage. How specifically modulate is not understood. Here, we investigate effects of on pre-catastrophe intermediate state dynamics, employing distinct substrates to mimic state. Surprisingly, find that CLASP1 promotes depolymerization stabilized presence GTP, but absence nucleotide. This activity also observed for CLASP2 family members a minimal TOG2-domain construct. Conversely, stabilizes unstable upon tubulin dilution GTP. Strikingly, our results reveal drives with vastly different inherent stabilities into same slowly depolymerizing nucleotide-dependent manner. We interpret this as Therefore, conclude suppress stabilizing

Язык: Английский

Процитировано

8
α-tubulin detyrosination fine-tunes kinetochore-microtubule attachments DOI Creative Commons
Hugo Girão, Joana Macário-Monteiro, Ana C. Figueiredo

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 9, 2024

Post-translational cycles of α-tubulin detyrosination and tyrosination generate microtubule diversity, the cellular functions which remain largely unknown. Here we show that regulates kinetochore-microtubule attachments to ensure normal chromosome oscillations timely anaphase onset during mitosis. Remarkably, detyrosinated levels near kinetochore plus-ends depend on direction motion metaphase. Proteomic analyses unveil KNL-1/MIS12/NDC80 (KMN) network forms core microtubule-binding site at kinetochores microtubule-rescue protein CLASP2 are enriched tyrosinated microtubules mitosis, respectively. enhances binding NDC80 complex diffusion along lattice in vitro. Rescue experiments overexpressing NDC80, including variants with slower diffusion, suggest a functional interplay for establishment labile interface. These results offer mechanistic explanation how different fine-tune load-bearing both growing shrinking microtubules.

Язык: Английский

Процитировано

2
Microtubule Regulation in Cancer Cells DOI

Alex Matov

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

2
Abl2 repairs microtubules and phase separates with tubulin to promote microtubule nucleation DOI Creative Commons
Daisy Duan,

Wanqing Lyu,

Pengxin Chai

и другие.

Current Biology, Год журнала: 2023, Номер 33(21), С. 4582 - 4598.e10

Опубликована: Окт. 18, 2023

Язык: Английский

Процитировано

5
Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends DOI Creative Commons
Lauren A McCormick, Joseph M. Cleary, William O. Hancock

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Июль 21, 2023

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The 'self-acting' (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas 'interface-acting' (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding 'poisoning' plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

Процитировано

4
Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends DOI Creative Commons
Lauren A McCormick, Joseph M. Cleary, William O. Hancock

и другие.

eLife, Год журнала: 2024, Номер 12

Опубликована: Янв. 5, 2024

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding ‘poisoning’ plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

Процитировано

1
Precise construction of DNA origami‐based materials for functional regulation on biological interface DOI Creative Commons
Yushuai Wu, Xiaohui Wu,

Run Tian

и другие.

Smart Molecules, Год журнала: 2024, Номер 2(1)

Опубликована: Март 1, 2024

Abstract Precise design and control of molecular self‐assembly as living creatures are exciting ideas in the field nanotechnology. Characterized with predesigned geometries accurate spatial addressability, programmable DNA origami nanostructures have been recognized optimized tools for assembling multiple functional components. A variety biomolecules can be attached to nanoscale drawing boards a site‐specific fashion, thus facilitating precise construction origami‐based materials studies on biological interface. In this minireview, we highlight recent advances artificial bio‐structures and/or biomimicking functions. The regulation functions by these origami‐engineered assemblies at bio‐interface has summarized discussed.

Язык: Английский

Процитировано

1