Scientists have determined the three-dimensional atomic structure of a protein that is important for organ functions.
The protein, called HIP14, is involved in the homeostasis of organelles, which are the cell’s tiny organ-like structures. HIP14 is essential for the recycling of lipid vesicles, tiny bubbles that play a key role in many cellular processes.
HIP14 belongs to a class of proteins called lipid transporters, which shuttle lipids around the cell. Defects in lipid transport are linked to a number of diseases, including cancer, diabetes, and Alzheimer’s disease.
The new study, published in the journal Nature, provides the first glimpse of how HIP14 works at the atomic level.
“Our results show how HIP14 inserts itself into membranes and how it uses its ‘paws’ to grip and release lipids,” said study co-lead author Jeffrey Duong, PhD, of the University of California, San Francisco (UCSF).
“This insight could lead to the development of drugs that specifically target HIP14 and other lipid transporters to treat diseases associated with lipid dysregulation.”
HIP14 is a type of protein known as a P-type ATPase. ATPases are enzymes that use energy from ATP, the cell’s energy currency, to power a variety of cellular processes.
P-type ATPases are found in all organisms and are responsible for a wide range of essential functions, from pumping calcium ions across cell membranes to regulating the acidity of organelles.
HIP14 is a P-type ATPase that is found in the endoplasmic reticulum (ER), a network of membranes that play a key role in lipid homeostasis.
The ER is responsible for manufacturing, storing, and transporting lipids. It is also the site of lipid remodeling, a process by which lipids are recycled and reused.
HIP14 is required for the recycling of lipid vesicles in the ER. Lipid vesicles are tiny bubbles that are formed when lipid molecules coalesce.
They play a key role in many cellular processes, including cell signaling, membrane trafficking, and lipid storage.
Lipid vesicles are constantly being formed and broken down in the ER. When a vesicle is no longer needed, it is recycled back into the ER membrane.
This process is known as lipid vesicle budding and is essential for maintaining the correct balance of lipids in the cell.
HIP14 is required for the release of lipid vesicles from the ER membrane. Without HIP14, the vesicles would become trapped in the membrane and would eventually be degraded.
“HIP14 is a key player in lipid homeostasis,” said study co-lead author Wei Lü, PhD, of UCSF.
“Lipid dysregulation is linked to a number of diseases, and understanding how HIP14 works at the atomic level could lead to the development of drugs that target this protein to treat these diseases.”
In a new study, researchers have determined the three-dimensional atomic structure of a protein important for organ functions.
This protein, called HtrA2, is a chaperone protein that helps other proteins fold correctly. Mutations in the HtrA2 gene have been linked to several diseases, including Parkinson’s disease, Alzheimer’s disease, and cancer.
Despite its importance, the three-dimensional structure of HtrA2 has remained elusive. In the new study, the researchers used a technique called cryo-electron microscopy to obtain a high-resolution 3D structure of HtrA2.
The results revealed that HtrA2 consists of four main domains: an N-terminal domain, a chaperone domain, an ATPase domain, and a PDZ domain. The PDZ domain is known to interact with other proteins, including the huntingtin protein linked to Huntington’s disease.
The 3D structure of HtrA2 provides new insights into how this protein functions and could be used to develop new drugs for the treatment of HtrA2-related diseases.
