Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Bonding for color

Unscrambling the link between molecular bonding and distributing pigment leads to potential therapeutics for a rare skin disease

A RIKEN-led team of molecular biologists has determined the specific bonding leading to the formation of a protein complex involved in distributing pigment throughout the skin. Disruption of this membrane transport complex leads to the rare, lethal Griscelli syndrome for which there is no effective treatment.

Patients show symptoms of albinism, suffer immunodeficiency, and typically die in early childhood. The work may stimulate the development of therapeutic drugs for the condition.

Members of the Rab protein family—of which there are more than 60 in humans—are thought to be essential to membrane trafficking, an important form of communication and distribution within cells. Rab proteins are typically bound to membranes either in an inactive guanine diphosphate form or an active triphosphate form which works through specific effector molecules to promote membrane trafficking.

The pigment melanin, which protects against radiation damage, is made and distributed within vesicles called melanosomes in skin color cells known as melanocytes. Rab27, which comes in two forms A and B, binds into a complex with the effector protein Slac2-a and myosin Va to transfer melanosomes onto actin filaments. The complex then transports the melanosomes along the filaments to where Rab27 uses another effector molecule to anchor them to the outer membrane of the cell.

Researchers from the RIKEN Systems and Structural Biology Center in Yokohama together with colleagues from Tohoku University were able to crystallize the Rab27B/Slac2-a complex and solve its structure using x-ray diffraction. As active Rab27 proteins are notoriously difficult to crystallize, this was the first mammalian complex where the binding of such a protein with its effector molecule could be thoroughly investigated. The results were published recently in the journal Structure1.

The researchers found three contact regions between Rab27B and Slac2-a, of which only one was involved in specific recognition. Mutations affecting any of the several specific intermolecular hydrogen bonds in this region were fundamentally disruptive, and some of them led to Griscelli’s syndrome. The group was able to verify the structure by taking another Rab protein, Rab3A, and engineering it to bind Slac2-a. The Rab3A amino acid sequence had to be altered by only four amino acid residues in the critical binding area to form the complex with Slac2-a.

“We are hoping that pharmaceutical companies will be able to use our structure as a basis for drugs which can be used to treat conditions like Griscelli’s syndrome,” says first author Mutsuko Kukimoto-Niino.


1. Kukimoto-Niino, M., Sakamoto, A., Kanno, E., Hanawa-Suetsugu, K., Terada, T., Shirouzu, M., Fukuda, M. & Yokoyama, S. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure 16, 1478–1490 (2008).

The corresponding author for this highlight is based at the RIKEN Systems and Structural Biology Research Center

Saeko Okada | ResearchSEA
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>