Signal boost uncovers hundreds of hidden binding partners for blood protein receptor

The quantity of each of the more than a thousand different glycoproteins in your blood varies considerably, the 10 most abundant glycoproteins representing 90% of the total mass. Finding a protein that is not in this top 10 is a bit like looking for Waldo if a single interpretation of the character remained in a collection of each comic strip “where’s waldo” never produced.

This range of disparities in the protein concentration is called dynamic range, and it is more difficult for scientists to identify less abundant proteins and their corresponding receptors.

Scientists from Sanford Burnham Prebys and colleagues from the Research Institute scripps have published results Nature communications Demonstrating a strategy to identify less abundant proteins that bind to a specific type of receiver called an endocyte lectin, and namely the MRC1 Mannose receiver (also known as CD206 and MMR). This approach allowed the research team to discover hundreds of binding partners who predicted the roles of MRC1 in our health.

To increase the signal and overcome the noise of so much protein appearing at different levels, the researchers used the Liaison Lectin with the Concanavaline A (CONA) mannosis to first enrich these blood proteins bearing several mannosis links.

“Cona and MRC1 both have the same Mannose bonding properties; however, MRC1 is not available as a similar recombinant protein,” said Mayank Saraswat, PH.D., main scientist at Sanford Burnham Prebys and study co-author.

“We have isolated proteins that bind to the cona of normal mouse and mouse plasma without MRC1,” said Saraswat. “The comparisons have revealed increased sensitivity and selectivity to identify the ligands of the receiver as they accumulate in the blood in the absence of MRC1.”

MRC1 maintains the concentration of various critical blood plasma proteins in a healthy beach. He does so by binding to proteins that have been changed post-translation with mannosis, sometimes called mannosylated proteins. The binding of MRC1 manosylated proteins initiates an endocyte clearance mechanism which limits the half ligands of the Ligand MRC1 and the abundance of circulation.

After comparing the proteins in the bloodstream circulation of normal mice and mice without MRC1, the team found the accumulation of 244 manosylated blood plasma proteins to double or more of the quantities found in normal mice due to MRC1 no longer maintains the levels in failure.

Scientists then examined the newly identified ligands more closely. They used bioinformatics to examine and represent these hundreds of proteins by their functions.

“We have noticed that many proteins had very important roles to play,” said Jamey Marth, Ph.D., professor at Sanford Burnham Prebys and senior author and correspondent for the manuscript. “The renin and angiotensin conversion enzymes, for example, are major blood pressure regulators.”

The researchers dug more deeply in eight of these proteins known to affect blood pressure, inflammation, the function of the organs and sepsis.

“We have observed the disturbance of normal physiology and function which were entirely predictable from the identity of the accumulation of manosylated proteins, with the additional effect of monitoring the disease with chronological age,” said Marth.

In the case of sepsis, mice devoid of MRC1 perished more quickly from the condition.

“When we examined the blood samples of patients with human septicemia, we found that there was a difference in proteins that accumulated compared to the deficient MRC1 mice,” said Saraswat. “However, when we compared the paths controlled by these proteins, half of the people activated in human sepsis were also activated by the dysfunction of the MRC-1.”

“To understand the part that glycosidic links play in health and disease by modifying the abundance and activity of blood glycoproteins, we must decipher this new language covering protein glycosylation, detect anomalies and determine how this system results in the body to affect different physiological functions,” said Saraswat.