Unique Hand-Over-Hand Rotation Transports Molecules
PA) - Within every neuron is a vast protein trail system
traversed by a small protein engine called Myosin V.
The long-standing question of how this molecule moves
may have finally been resolved by researchers from the
University of Pennsylvania School of Medicine.
Their findings, presented in this week's issue of Nature,
show how myosin V can move 'hand-over-hand' on tracks,
composed of a protein called actin, without completely
letting go at any point. According to the researchers,
myosin V offers a fascinating example of how cells convert
chemical energy into motion, and may offer a natural
example of molecular motors for the purposes of nanotechnology.
"There are a number of theories on how
this molecule moves. What concerned me was how this
little myosin motor can move along the track without
letting go and floating off into the cytoplasm of the
cell," said Yale E. Goldman, MD, PhD, professor
in Penn's Department of Physiology and director of the
Pennsylvania Muscle Institute (PMI). "It turns out that
myosin tilts as it steps along the actin track - one
head attaches to the track and then the molecule rotates
allowing the other head to attach - much like a child
on a playground crosses the monkey-bars hand-over-hand."
Myosin V, which is also found in pigment
cells, is a protein that consists of two heads attached
to a long tail, which can bind to the motor's molecular
'cargo.' Myosin travels over long filaments of a protein
called actin. This cytoskeletal network is a feature
of all multicellular creatures, and it is used to transport
molecules throughout a single cell. In humans, Griscelli
disease, which is characterized by neurological deficits
and a lack of pigment, stems from non-functioning myosin
Goldman and his colleagues were able to
study the hand-over-hand motion of a single myosin motor
in action thanks to an innovative microscopic technique
created by Joseph N. Forkey, PhD, a post-doctoral
researcher at Goldman's PMI laboratory. The technique,
called single-molecule fluorescence polarization, involved
labeling myosin V with a fluorescent tag. The researchers
then used a laser beam to hit the tag, creating an electromagnetic
field that could resolve the angle at which the molecule
"Using single-molecule fluorescence polarization,
we could detect the three-dimensional orientation of
myosin V tilting back and forth between two well-defined
angles as it teetered along," said Goldman.
Researchers contributing to this work
include Margot E. Quinlan and M. Alexander Shaw of PMI
and John E. T. Corrie of the National Institute for
Medical Research in London, UK.
This research was supported by grants
from the National Institutes of Health and the Medical
# # #
Editor's Note: Click here
for an illustration of myosinV in motion.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year.
The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided $500 million to benefit our community.