S100A1

Description

The S100A1 (S100 calcium binding protein A1) is a protein-coding gene located on chromosome 1.

S100A1, also known as S100 calcium-binding protein A1, is a protein encoded by the S100A1 gene in humans. It is highly expressed in cardiac and skeletal muscle, localizing to Z-discs and sarcoplasmic reticulum. S100A1 has shown potential as a gene therapy candidate for treating post-myocardially infarcted cardiac tissue. S100A1 is a member of the S100 family of proteins expressed in cardiac muscle, skeletal muscle, and brain, with highest density at Z-lines and sarcoplasmic reticulum. It contains 4 EF-hand calcium-binding motifs in its dimerized form and can exist as either a hetero or homodimer. The S100A1 homodimer has high affinity (nanomolar range or tighter), formed through hydrophobic packing of an X-type 4-helix bundle created between helices 1, 1', 4, and 4'. Nuclear magnetic resonance spectroscopy structural information on the homodimeric form reveals that each monomer is helical and contains two EF-hand calcium-binding loops: one in the N-terminus and a canonical EF hand in the C-terminus with higher calcium affinity (dissociation constant of roughly 20 micromolar). These two EF hand domains are spatially close and connected through a short beta sheet region (residues 27–29 and 68–70). Upon calcium binding, helix 3 of S100A1 reorients from being relatively antiparallel to helix 4 to being roughly perpendicular. This conformational change is unique, as the entering helix, and not the exiting helix, moves.

S100A1 is a small calcium-binding protein that plays crucial roles in various biological processes, including calcium homeostasis, chondrocyte biology, and cardiomyocyte regulation. When intracellular calcium levels rise, S100A1 binds calcium, triggering conformational changes. These changes enable interactions with specific target proteins, ultimately modulating their activity. In cardiomyocytes, S100A1 regulates a network that controls sarcoplasmic reticulum calcium cycling and mitochondrial function. This regulation is achieved through interactions with the ryanodine receptors RYR1 and RYR2, sarcoplasmic reticulum calcium-ATPase/ATP2A2, and mitochondrial F1-ATPase. S100A1 facilitates diastolic calcium dissociation and myofilament mechanics, leading to improved relaxation during diastole.

S100A1 is also known as S100, S100-alpha, S100A.

Associated Diseases

WES Whole Exome Sequencing