SPLUNC1: How lungs protect themselves from infection

December 01, 2014

Scientists have taken an important step toward a new class of antibiotics aimed at stopping lung infections. They found that a protein found in large airways, called "SPLUNC1," binds to lipids critical to defending against bacterial and viral infections, as well as keeping lung tissue flexible and hydrated. This discovery moves SPLUNC1 closer toward becoming a viable therapy and was reported in the December 2014 issue of The FASEB Journal.

"By shedding light on the mechanisms and interactions between various elements of pulmonary surfactant, our findings represent significant headway toward developing novel treatments for a variety of pulmonary diseases," said Gongyi Zhang, Ph.D., a researcher involved in the work from the Department of Biomedical Research at National Jewish Health in Denver, Colorado. "We anticipate that our study will bring us closer to transforming SPLUNC1 into a promising therapeutic option to help asthma and COPD patients clear bacterial and viral infections from the airway."

To make this discovery, Zhang and colleagues overexpressed and crystallized the SPLUNC1 protein. The three dimensional molecular structure of SPLUNC1 was then determined using x-ray crystallography. Next, its structure was compared to existing structures of a similar antibacterial protein (homolog), called the "bactericidal/permeability-increasing protein" or BPI. The researchers found a dramatic surface charge difference between SPLUNC1 and BPI, suggesting that SPLUNC1 and BPI have different lipid ligands. Finally, a lipid ligand, dipalmitoyl-phosphatidylcholine, or DPPC, was found to bind specifically to SPLUNC1. And DPPC is the surfactant that our lungs use to keep airways open. This sheds new light on the way SPLUNC1 functions in the human airway and the structural information uncovered allows for a better understanding of its properties and potential.

"The way to live forever is simple: Don't stop breathing," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The problem is that this isn't as easy as it sounds, especially for people with serious lung diseases and infections. This report offers hope that even some of the most difficult infections, from MRSA to Pseudomonas, can be treated in the future."
-end-
Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is the world's most cited biology journal according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.

FASEB is composed of 27 societies with more than 120,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Details: Fangkun Ning, Chao Wang, Karin Zemski Berry, Pitchaimani Kandasamy, Haolin Liu, Robert C. Murphy, Dennis R. Voelker, Chu Won Nho, Choel-Ho Pan, Shaodong Dai, Liwen Niu, Hong-Wei Chu, and Gongyi Zhang. Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands. FASEB J. December 2014 28:5349-5360; doi:10.1096/fj.14-259291 ; http://www.fasebj.org/content/28/12/5349.abstract

Federation of American Societies for Experimental Biology

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.