[GRG] NewAbs: The Story of Actin Proteins

To Members and Friends of the Los Angeles Gerontology
Research Group:  The story
of actin… — Steve Coles

“Biologists Take Snapshot of
Fleeting Protein Process”

 

Actin was discovered in 1887, but scientists have struggled to unlock
some of the polymer?s secrets. In a newly published study, scientists
from Rice University and Baylor College of Medicine describe the
completion this year of the first structural analysis of the actin
nucleus, the first two actin monomers that come together to form the
basis of an actin filament. Image: J. Ma/Rice University  

Friday, May 31, 2013; (R&D) — Structural biologists from
Rice University and Baylor College of Medicine (BCM) have
captured the first 3-D crystalline snapshot of a critical but fleeting
process that takes place thousands of times per second in each human
cell. The research appears on-line in Cell Reports and could prove
useful in the study of cancer and other diseases.The
biological ?freeze-frame? shows the initial step in the formation of
actin, a sturdy strand-like filament that is vital for humans. Actin
filaments help cells maintain their shape. The filaments, which are
called F-actin, also play key roles in muscle contraction, cell division
and other critical processes.?One of
the major distinctions between cancerous cells and healthy cells is their
shape,? says study co-author Jianpeng Ma, professor of bioengineering at
Rice and the Lodwick T. Bolin Professor of Biochemistry at BCM. ?There is
a correlation between healthy shape and well-regulated cell growth, and
cancer cells are often ugly and ill-shaped compared to healthy
cells.?F-actin
was discovered in 1887, but despite the more than 18,000 actin-related
studies in scientific literature, biologists have struggled to unlock
some of its secrets. For example, F-actin is a polymer made of many
smaller proteins called monomers. These building blocks, which are called
G-actin, self-assemble end to end to form F-actin. But the self-assembly
process is so efficient that scientists have been unable to see what
happens when the first two or three monomers come together to form the
nucleus of a filament. The F-actin filaments inside cells are constantly
being built, torn apart and rebuilt.

 

To decipher the structure of the F-actin nucleus, researchers used a
dual-mutant strategy. They created two mutant versions of actin monomers
that could bind together to form a nucleus but could not bind with
additional monomers to form the F-actin polymer chain. Image: J. Ma/Rice
University  
?Nucleation is critical for this continual building and rebuilding,? says
BCM biochemist and study co-author Qinghua Wang. ?For healthy cells,
nucleation is the starting place for robust shape. For unhealthy cells,
like cancer, nucleation processes may play a crucial role in unregulated
growth. That?s one reason we want to better understand
nucleation.?In 2008,
Ma and Wang asked Xiaorui Chen, a graduate student in BCM?s Structural
and Computational Biology and Molecular Biophysics program, to undertake
the task of using x-ray crystallography to determine the structure of the
actin nucleus. Her initial attempts failed, but the team finally hit upon
the winning idea of creating two mutant versions of G-actin that could
nucleate but not polymerize.Native
G-actin binds with one neighbor on top and one on bottom, and this
top-bottom, end-to-end binding pattern is the key to forming long F-actin
polymers. To foster nucleation without polymerization, Chen created two
mutant versions of G-actin. One mutant could bind normally on top but not
on bottom, and the other could bind normally on bottom but not on
top.?This
dual-mutant strategy was the key,? says Chen, who is now a postdoctoral
researcher at BCM. ?After that, we had to overcome problems related to
forming and growing the crystal samples needed for
crystallography.?Chen used
a two-stage process to prepare the crystals. She first used high levels
of super-saturation to spur initial crystal formation and then used a
process called seeding to transfer the newly formed crystals to another
medium where they could grow large enough for examination.Once the
crystals were prepared, they were analyzed with x-ray diffraction, which
revealed the atomic arrangement of each atom in the nucleated,
dual-mutant pair. ?We believe this dual-mutant arrangement reveals the
most critical contacts involved in nucleation,? Ma says. ?For the first
time, we are able to see how actin nucleation begins.?Source:

Rice University
Topics:

R &
D Daily

Beam Analysis

Biology

Biology

Genomics & Proteomics

L. Stephen Coles, M.D., Ph.D., Co-Founder
Los Angeles Gerontology Research GroupURL:
http://www.grg.org
E-mail: scoles@grg.orgE-mail:
scoles@ucla.edu

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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