With the aid of evolutionary clues, scientists have determined the complex process involved in blood clotting after injury.
The finding by scientists at Washington University School of Medicine in St. Louis reveals how a key clotting protein assembles, providing new light on common bleeding disorders.
The long tube-shaped protein with a vital role in blood clotting is called von Willebrand Factor (VWF).
Made in cells that form the inner lining of blood vessels, VWF circulates in the blood seeking out sites of injury.
When it finds them, its helical tube unfurls to catch platelets and form blood clots.
Defects in VWF cause von Willebrand Disease, the most common inherited bleeding disorder in humans.
"The challenge for the cell is how to build this massive protein without clogging the machinery," said J. Evan Sadler, MD, PhD, professor of medicine and senior author of the study.
"The cell has solved this problem by making the assembly of von Willebrand Factor dependent on its location in the cell.
"Without VWF, you bleed," he added.
For their finding, Sadler and his team looked to evolution.
Sadler's group gathered the DNA sequences of VWF for humans, 19 other placental mammals, a marsupial, two birds, a reptile, an amphibian and five fish.
The study was published in July in the Journal of Biological Chemistry.