Experimental and computational approaches yield a high-resolution, 1-Mb physical map of the region harboring the mouse t haplotype sterility factor, tcs1

2001 ◽  
Vol 12 (8) ◽  
pp. 668-670 ◽  
Author(s):  
Antonio Planchart ◽  
John C. Schimenti
2018 ◽  
Author(s):  
Elizabeth H. Kellogg ◽  
Nisreen M.A. Hejab ◽  
Simon Poepsel ◽  
Kenneth H. Downing ◽  
Frank DiMaio ◽  
...  

AbstractTau is a developmentally regulated protein found in axons, whose physiological role is to stabilize and bundle microtubules (MTs). Hyper-phosphorylation of tau is thought to cause its detachment from MTs and subsequent aggregation into pathological fibrils that have been implicated in Alzheimer’s disease pathogenesis. Despite its known MT binding role, there is no consensus regarding which tau residues are crucial for tau-MT interactions, where on the MT tau binds, and how binding results in MT stabilization. We have used cryo-EM to visualize the interaction of different tau constructs with MTs at high resolution (3.2-4.8 Å) and used computational approaches to generate atomic models of tau-tubulin interactions. Our work shows that the highly conserved tubulin-binding repeats within tau adopt very similar structures in their interactions with the MT. Each tau repeat binds the MT exterior and adopts an extended structure along the crest of the protofilament (PF), interacting with both α- and β-tubulin, thus stabilizing the interface between tubulin dimers. Our structures agree with and explain previous biochemical data concerning the effect of phosphorylation on MT affinity and lead to a model in which tau repeats bind in tandem along a PF, tethering together tubulin dimers and stabilizing longitudinal polymerization interfaces. These structural findings could establish a basis of future treatments aiming at the selective stabilization of tau-MT interactions.


2001 ◽  
Vol 12 (5) ◽  
pp. 380-386 ◽  
Author(s):  
Annie Robic ◽  
Jin-Tae Jeon ◽  
Virginie Rey ◽  
Valérie Amarger ◽  
Patrick Chardon ◽  
...  

Genomics ◽  
1997 ◽  
Vol 44 (2) ◽  
pp. 214-221 ◽  
Author(s):  
Bora E. Baysal ◽  
Evert M. van Schothorst ◽  
Joan E. Farr ◽  
Michael R. James ◽  
Peter Devilee ◽  
...  

2002 ◽  
Vol 1 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Madan Thangavelu ◽  
Allan B. James ◽  
Alan Bankier ◽  
Glenn J. Bryan ◽  
Paul H. Dear ◽  
...  

2005 ◽  
Vol 16 (8) ◽  
pp. 631-649 ◽  
Author(s):  
Candice Brinkmeyer-Langford ◽  
Terje Raudsepp ◽  
Eun-Joon Lee ◽  
Glenda Goh ◽  
Alejandro A. Schäffer ◽  
...  

DNA Research ◽  
2014 ◽  
Vol 22 (1) ◽  
pp. 39-52 ◽  
Author(s):  
Y. Li ◽  
S. Liu ◽  
Z. Qin ◽  
G. Waldbieser ◽  
R. Wang ◽  
...  

1999 ◽  
Vol 9 (7) ◽  
pp. 662-671
Author(s):  
Vundavalli V.V.S. Murty ◽  
Kate Montgomery ◽  
Shipra Dutta ◽  
Shashi Bala ◽  
Beatrice Renault ◽  
...  

Cytogenetic and molecular genetic analyses have shown that the 12q22 region is recurrently deleted in male germ cell tumors (GCTs), suggesting that this site may harbor a tumor suppressor gene (TSG). Previous loss of heterozygosity (LOH) analyses identified a consensus minimal deleted region between the markers D12S377 andD12S296, and a YAC clone contig covering the region was generated. Here, we describe a high-resolution sequence-ready physical map of this contig covering a 3-Mb region. The map comprised of 52 cosmids, 49 PACs, and 168 BACs that were anchored to the previous YAC contig; 99 polymorphic, nonpolymorphic, EST, and gene-based markers are now placed on this map in a unique order. Of these, 61 markers were isolated in the present study, including one that was polymorphic. In addition, we have narrowed the minimal deletion to ∼830 kb betweenD12S1716 (proximal) and P382A8-AG (distal) by LOH analysis of 108 normal-tumor DNAs from GCT patients using 21 polymorphic STSs. These physical and deletion maps should prove useful for identification of the candidate TSG in GCTs, provide framework to generate complete DNA sequence, and ultimately generate a gene map of this segment of the chromosome 12.[The sequence data described in this paper have been submitted to the Genome Survey Sequence under accession nos. AQ254896–AQ254955 andAQ269251–AQ269266. Online supplementary material is available athttp://www.genome.org]


Sign in / Sign up

Export Citation Format

Share Document