APOL1 - Apolipoprotein L1 | Elisa - Clia - Antibody - Protein

Background:

Apolipoprotein L1 (APOL1) is a protein encoded by the APOL1 gene in humans. It plays a significant role in lipid metabolism and innate immunity. The APOL1 gene has been associatied to certain kidney diseases, particularly in individuals of African descent. Variants in the APOL1 gene are strongly linked to an increased risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) The two most common variants associated with kidney disease are G1 and G2. These variants are found almost exclusively in people with recent African ancestry and are thought to have arisen as a defense mechanism against African sleeping sickness, caused by the parasite Trypanosoma brucei rhodesiense. However, these variants also increase susceptibility to certain forms of kidney disease. The exact mechanisms by which APOL1 variants lead to kidney damage are not fully understood. However, research suggests that the expression of APOL1 G1 and G2 variants in kidney cells can lead to cell injury and death, ultimately contributing to the development of kidney disease.The presence of APOL1 risk variants is associated with an increased risk of kidney disease progression and poorer outcomes in individuals with CKD or other kidney disorders. Understanding a patient's APOL1 genotype can help clinicians better assess their risk of kidney disease and tailor treatment strategies accordingly.

Protein Structure:

• Primary Structure: APOL1 consists of approximately 398 amino acids.
• Secondary Structure: The protein contains multiple alpha helices and beta sheets that contribute to its functional domains.
• Tertiary Structure: APOL1 has a complex tertiary structure that includes lipid-binding domains and regions responsible for its interaction with cellular membranes.
• Quaternary Structure: It can form homodimers and heterodimers, particularly when interacting with other proteins or lipoprotein particles.

Classification and Subtypes:

APOL1 is part of the apolipoprotein L family, which includes several other apolipoproteins with similar functions. There are different isoforms of APOL1 resulting from alternative splicing, but the most studied variants are related to the gene's polymorphisms.

Function and Biological Significance:

• Lipid Transport: APOL1 is involved in the transport of lipids, particularly within HDL particles, contributing to cholesterol homeostasis and reverse cholesterol transport.
• Immune Response: APOL1 has a role in the innate immune system. It can lyse certain trypanosome species by forming pores in their membranes, protecting against African sleeping sickness.
• Kidney Function: APOL1 is highly expressed in the kidney, where it is involved in podocyte function and the maintenance of glomerular filtration. Genetic variants of APOL1 have been linked to an increased risk of kidney diseases, including focal segmental glomerulosclerosis (FSGS) and hypertension-attributable end-stage renal disease (ESRD).

Interactions:

• Lipoprotein Interactions: APOL1 is a component of HDL particles and interacts with other apolipoproteins and lipids within these complexes.
• Membrane Binding: APOL1 can bind to cellular membranes, particularly in its role in lysing trypanosomes.
• Protein Interactions: APOL1 interacts with other proteins involved in lipid metabolism and immune response, including various receptors and transporters on the surface of cells.

Clinical Issues:

• Kidney Disease: Genetic variants of APOL1, specifically the G1 and G2 alleles, are strongly associated with an increased risk of kidney diseases, including FSGS and ESRD. These variants are more common in individuals of African descent and are thought to confer a selective advantage against trypanosomiasis.
• Cardiovascular Disease: The role of APOL1 in lipid transport and immune response suggests that it may also be involved in cardiovascular health, although its precise contributions require further study.
• Trypanosomiasis Resistance: APOL1 provides a protective effect against certain trypanosome species, contributing to its evolutionary significance.

Summary:

Apolipoprotein L1 (APOL1) is a crucial protein involved in lipid transport, immune response, and kidney function. It is a component of HDL particles and plays a role in cholesterol homeostasis and protection against trypanosome infections. Genetic variants of APOL1 are linked to an increased risk of kidney diseases, particularly in individuals of African descent. Understanding APOL1's functions and interactions is essential for developing therapeutic strategies for kidney diseases and exploring its role in cardiovascular health and immune protection.