S100 proteins represent a widespread family of proteins found throughout the body, playing diverse roles in maintaining cellular balance and function. These proteins are involved in a variety of fundamental biological activities, contributing to the healthy operation of numerous tissues and organs. Their activity is interconnected with many processes that ensure proper body function.
Understanding S100 Proteins
S100 proteins are small, calcium-binding proteins, weighing between 10 and 14 kilodaltons (kDa). This family consists of at least 21 distinct members, such as S100B and various S100A family proteins, each with specific tissue and cell type expression patterns.
A defining feature of S100 proteins is their ability to bind calcium ions through specialized helix-loop-helix structures known as “EF-hand” motifs. S100 proteins possess two such calcium-binding sites. The binding of calcium ions induces a change in the protein’s shape, exposing a hydrophobic surface. This conformational shift allows S100 proteins to interact with and regulate the activity of other proteins within the cell.
Key Functions in the Body
S100 proteins are involved in intracellular and extracellular functions. Within cells, they act as calcium sensors, translating external stimuli into specific cellular responses by interacting with various target proteins. These interactions influence processes like protein phosphorylation, the regulation of transcription factors, and maintaining calcium balance.
S100 proteins also play a role in the dynamics of cellular components, such as the cytoskeleton, which provides structural support to cells. They influence enzyme activities, contributing to metabolic pathways, including energy metabolism. S100 proteins can be released from cells and act as signaling molecules, regulating functions in neighboring cells and participating in the inflammatory response.
This family of proteins contributes to fundamental cellular behaviors like cell growth, differentiation, and movement. Their involvement in these processes maintains cellular health and function.
S100 Proteins and Disease
Altered levels of specific S100 proteins can serve as indicators for diseases and conditions. These proteins are often released from cells following tissue damage or cellular stress, making their extracellular presence a sign of underlying issues. The levels of S100 proteins in body fluids like serum, cerebrospinal fluid, and urine can provide insights into disease progression or injury severity.
Brain Injury
S100B, a specific S100 protein predominantly found in astrocytes within the central nervous system, is a widely studied biomarker for brain injury. Elevated S100B levels in cerebrospinal fluid and blood can indicate damage to brain tissue, such as in traumatic brain injury (TBI) and stroke. After severe TBI, mean peak S100B levels in both cerebrospinal fluid and serum typically occur on day zero (the day of injury) and remain elevated compared to healthy controls for several days.
While S100B can be elevated due to injuries outside the brain, it is a recognized neurobiochemical marker for nervous system damage. Its measurement in the acute phase following a traumatic event can help clinicians assess the need for further imaging, such as CT scans, potentially reducing unnecessary procedures. Depending on its concentration, S100B can have both beneficial (neurotrophic) and harmful (neurotoxic) effects on cells.
Melanoma
S100B is also a recognized biomarker for monitoring melanoma, a type of skin cancer. Melanoma cells can shed S100B, and its levels in the peripheral blood have been investigated for their prognostic value in predicting disease relapse and mortality risk. A higher baseline S100B level or an increase in S100B during follow-up can suggest a greater risk of recurrence and may prompt further evaluation to detect subclinical disease.
While an elevated serum S100B level (e.g., ≥0.15 µg/L) has a high positive predictive value for disease recurrence, indicating that recurrence is likely when levels are high, its sensitivity for detecting recurrence is lower. This means that a normal S100B level does not rule out disease recurrence. Nevertheless, rising S100B values, even within the normal range, can be an important clue to disease progression in patients with high-risk melanoma.
Neurodegenerative and Inflammatory Conditions
S100 proteins are also linked to neurodegenerative diseases, where they are associated with neuroinflammation. For instance, S100B levels are often altered in conditions like Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). In these disorders, S100B can contribute to the pathogenic processes, and its altered levels may correlate with the progression of clinical symptoms.
Beyond neurological conditions, S100 proteins are involved in inflammatory processes throughout the body. Certain S100 proteins, such as S100A8, S100A9, and S100A12, act as danger signals that activate immune cells and endothelial cells, modulating inflammatory responses. Their involvement highlights their broader role in the body’s response to stress and injury.