Nanotechnology Now







Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > Unsung Hero – Berkeley researchers produce high-res model of Ndc80 in action

Overhead view of a subnanometer resolution reconstruction showing the microtubule-binding region of the Ndc80 complex (blue) attached to a microtubule(green). The part of the Ndc80 complex away from the microtubule is flexible and appears as scattered density in the reconstruction (red). (Image courtesy of Nogales group)
Overhead view of a subnanometer resolution reconstruction showing the microtubule-binding region of the Ndc80 complex (blue) attached to a microtubule(green). The part of the Ndc80 complex away from the microtubule is flexible and appears as scattered density in the reconstruction (red). (Image courtesy of Nogales group)

Abstract:
Unless you are in a field of study related to cell biology, you most likely have never heard of Ndc80. Yet this protein complex is essential to mitosis, the process by which a living cell separates its chromosomes and distributes them equally between its two daughter cells. Now, through a combination of cryo-electron microscopy and three-dimensional image reconstruction, a team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have produced a subnanometer resolution model of human Ndc80 that reveals how this unsung hero carries out its essential tasks.

Unsung Hero – Berkeley researchers produce high-res model of Ndc80 in action

Berkeley, CA | Posted on October 13th, 2010

"Our model suggests that Ndc80 oligomerizes on the surface of the microtubule via a segment of the protein that is regulated so that correct attachments are maintained and incorrect attachments are discarded," says biophysicist Eva Nogales who led this study.

"What we propose is that this oligomerization is an important part of the mechanism by which Ndc80 is able to utilize the energy of microtubule disassembly to move chromosomes towards the spindle poles during mitosis. This oligomerization will only happen for correctly attached microtubules"

Nogales holds joint appointments with Berkeley Lab's Life Sciences Divisions, UC Berkeley's Molecular and Cell Biology Department, and the Howard Hughes Medical Institute. An expert on electron microscopy and image analysis and an authority on the structure and dynamics of microtubules, she is the corresponding author of a paper published in the journal Nature titled, "The Ndc80 kinetochore complex forms oligomeric arrays along microtubules."

Co-authoring the paper with Nogales were Gregory Alushin, Vincent Ramey, Sebastiano Pasqualato, David Ball, Nikolaus Grigorieff and Andrea Musacchio.

Biological cells have a cytoskeleton that gives shape to membrane walls and other cellular structures and also controls the transportation of substances in and out of the cell. This cytoskeleton is spun from tiny fibers of tubulin protein called microtubles. During mitosis, microtubules disassemble and reform into spindles across which duplicate sets of chromosomes line up and migrate to opposite poles. After chromosome migration is complete, the microtubules disassemble and reform back into skeletal systems for the two new daughter cells.

Mistakes in the distribution of chromosomes from a parent cell to its daughter cells can lead to birth defects, cancer and other disorders. To ensure that each daughter cell receives a single copy of each chromosome, microtubule spindles dock with each chromosome's centromere - the central region where its two chromatids connect. The microtubule spindles connect with the centromere through a network of proteins called the kinetochore. Ndc80 is a key member of the kinetochore network and serves as a sort of "landing pad" for the microtubule-centromere connection. Although Ndc80's genetics and biochemistry have been extensively characterized, the mechanisms behind its activities have until now remained a mystery.

"Our first ever subnanometer model of Ndc80 shows that the protein complex binds the microtubule with a tubulin monomer repeat that is sensitive to tubulin conformation," Nogales says. "Furthermore, Ndc80 complexes self-associate along microtubule protofilaments via interactions that are mediated by the amino-terminal tail of the Ndc80 protein, which is the site of phospho-regulation by the Aurora B kinase."

The Aurora B kinase is an enzyme that ensures the correction of any improper microtubule-kinetochore attachments - faulty attachments will result in unequal segregation of the genetic material, such as both chromatides going to the same daughter cell. In their paper, Nogales and her co-authors contend that Ndc80's mode of interaction with the microtubule and its oligomerization provide a means by which the Aurora B kinase can regulate the stability of the load-bearing Ndc80-microtubule attachments.

"The Aurora B kinase corrects wrong microtubule-kinetochore attachments by phosphorylating proteins in the kinetochore," Nogales says. "Ndc80 is a major substrate of this regulation. Our work shows that if phosphorylated by Aurora B, attachments are not robust because there is no oligomerization of Ndc80s."

This research was supported by a grant from the National Institute of General Medical Sciences.

####

About Berkeley Lab
Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research for DOE’s Office of Science and is managed by the University of California. Visit our Website at www.lbl.gov/

For more information, please click here

Contacts:
Lynn Yarris
(510) 486-5375

Copyright © Berkeley Lab

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Hong Kong Investors Bullish on Dais Analytic Invest $5.75M, Provide $60M Contract, and Create New Joint Venture Company March 26th, 2015

Industrial Nanotech, Inc. Announces Next Large Order from the Oil and Gas Industry March 26th, 2015

Quantum compute this -- WSU mathematicians build code to take on toughest of cyber attacks: Revamped knapsack code offers online security for the future March 26th, 2015

Thousands of atoms entangled with a single photon: Result could make atomic clocks more accurate March 26th, 2015

Nanomedicine

Application of Graphene Oxide in Body Implants in Iran March 26th, 2015

Nanorobotic agents open the blood-brain barrier, offering hope for new brain treatments March 25th, 2015

Nanotechnology in Medical Devices Market is expected to reach $8.5 Billion by 2019 March 25th, 2015

Iranian Scientists Eliminate Expensive Materials from Diabetes Diagnosis Sensors March 25th, 2015

Announcements

Industrial Nanotech, Inc. Announces Next Large Order from the Oil and Gas Industry March 26th, 2015

Quantum compute this -- WSU mathematicians build code to take on toughest of cyber attacks: Revamped knapsack code offers online security for the future March 26th, 2015

Thousands of atoms entangled with a single photon: Result could make atomic clocks more accurate March 26th, 2015

Square ice filling for a graphene sandwich March 26th, 2015

Tools

FEI Technology Award of the German Neuroscience Society Goes to Benjamin Judkewitz of the University of Berlin: Bi-annual award honors excellence in brain research during the German Neuroscience Society’s Annual Meeting, held 18-21 March 2015 March 26th, 2015

Square ice filling for a graphene sandwich March 26th, 2015

Renishaw reports on the use of Raman spectroscopy at CNRS Orléans to study materials under extreme conditions March 25th, 2015

Nanorobotic agents open the blood-brain barrier, offering hope for new brain treatments March 25th, 2015

Grants/Awards/Scholarships/Gifts/Contests/Honors/Records

FEI Technology Award of the German Neuroscience Society Goes to Benjamin Judkewitz of the University of Berlin: Bi-annual award honors excellence in brain research during the German Neuroscience Society’s Annual Meeting, held 18-21 March 2015 March 26th, 2015

FEI Announces Image Contest Grand Prize Winner: Francisco Rangel of the National Institute of Technology, INT/MCTI, Brazil, wins the contest with his “Expanded Vermiculite” image March 23rd, 2015

Halas, Nordlander awarded Optical Society's R.W. Wood Prize: Rice University researchers recognized for pioneering nanophotonics March 21st, 2015

Hiden Instruments identified in London Stock Exchange’s ‘1000 Companies to Inspire Britain' March 21st, 2015

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More










ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







© Copyright 1999-2015 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE