Death due to lung inflammation has increased 31 percent over the last 35 years. A protein that influences this mortality rate is aquaporin‐4. This tetramer protein is a water channel that is water permeable. This integral protein, made up of six transmembrane helices and two pore helices, creates an hourglass shape. The structure of aquaporin is vital to its function due to pore helices preventing large molecules from passing through the membrane, only facilitating the movement of water molecules or small solutes. These two pore helices allow one molecule to pass at a time, making the net water movement facilitation easier. All types of aquaporins have NPA (asparagine‐proline‐alanine) motifs which are located in the central channel and are responsible for water permeation and intracellular processing. In aquaporin‐4, there are two NPA motifs at residues 97–99 and 213–215. Scientists discovered that aquaporin's response to bacterial stimuli can alter its pore size. Trauma, toxins or injury to tissue can cause a cell to become hypotonic. Aquaporin‐4 is specifically related to lung injury and inflammation because it is highly expressed in humans. The HUHS MAPS Team (Modeling A Protein Story) has designed a model of the wild form of AQP4 with 3D printing technology to investigate structure‐function relationships. The extensive research on aquaporins in relation to lung inflammation can contribute to the scientific and medical world and eventually target new pharmacological therapies.Support or Funding InformationThe MSOE Center for BioMolecular Modeling would like to acknowledge and thank the National Institutes of Health Clinical and Translational Science Award (NIH_CTSA UL1RR031973) and the Milwaukee School of Engineering for their support in funding the 2018_2019 SMART Team program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Mistakes in alternative splicing of RNA cause diseases such as acute myeloid leukemia. Serine Rich Splicing Factor 2 (SRSF2) is a splicing factor that controls alternative splicing by promoting exon inclusion, so it is not surprising that mutations to SRFS2 are linked to cancers. SR proteins harbor an RNA recognition motif (RRM) at the N‐terminus that binds to mRNA. SRSF2 has the unusual ability to bind to both pyrimidine and purine rich RNA sequences by flipping two C or G nucleotides in the mRNA into anti or syn orientations. The RRM specifically recognizes only C2, C3, and G5. Arg61 forms a hydrogen bond to C3, Phe59 hydrogen bonds to C2, and Lys17 is involved in flipping C2 or G2 into syn or anti conformations. Tyr92 binds with C2 and forms a hydrogen bond with C3. The mutation Pro95His binds better to UCCAGU and has been linked to cancer. The Hartford Union High School SMART (Students Modeling A Research Topic) Team modeled SRSF2 using 3D printing technology to highlight structural characteristics involved in RNA binding. Additional research on SRSF2 mutations and sequence binding has the potential to find both causes of and treatments for diseases like cancer.Support or Funding InformationThe MSOE Center for BioMolecular Modeling would like to acknowledge and thank the National Institutes of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973) for their support in funding the 2017‐2018 SMART Team Team program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Almost 20% of children who die of Sudden Infant Death Syndrome have a protein called Toxic Shock Syndrome Toxin‐1 (TSST‐1), produced by Staphylococcus aureus. This protein is also responsible for toxic shock and food poisoning. S. aureus produces this superantigen TSST‐1 to divert the immune system and multiply rapidly inside the body. TSST‐1 contains 194 amino acids and three domains. Identical domains A, B, and C consist of a larger alpha‐helix, residues 152‐168, along with two beta‐sheets, and three shorter alpha helices. The long alpha helix defines the protein as a superantigen. Antigen‐presenting cells, such as macrophages, contain Major Histocompatibility Complex class II. These domains are bound to T‐cell receptor beta sheets by TSST‐1, bypassing the normal interface, and activating up to 24% more than the average immune response. Despite TSST‐1 having no disulfide bridges, therefore lack of thermal denaturation resistance, TSST‐1 thrives in the human body due to an immune system distraction. TSST‐1 can move through mucous membranes, allowing S. aureus to disrupt the immune response without being inside the body. In the wild form of TSST‐1, His‐135 located adjacent to the long alpha‐helix is mutated to Alanine, creating mutant TSST‐1, making the superantigen inactive for reasons unknown. The HUHS SMART Team (Students Modeling A Research Topic) Team has designed a model of the wild form of TSST‐1 with 3D printing technology to investigate structure_function relationships. By studying how TSST‐1 interacts with the immune system, advances can be made to control the spread of these pyrogenic toxin superantigens.Support or Funding InformationThe MSOE Center for BioMolecular Modeling would like to acknowledge and thank the National Institutes of Health Clinical and Translational Science Award (NIH_CTSA UL1RR031973) and the Milwaukee School of Engineering for their support in funding the 2018_2019 SMART Team program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Spinal muscular atrophy (SMA) is a genetic disorder leading to death before age two. This is caused by degeneration of motor neurons in the spine and affects one in six thousand babies yearly (Families of SMA, 2013). It is unknown why a point mutation or deletion of the SMN1 gene, which produces survival motor neuron (SMN) protein, causes degeneration. The SMN complex is made of SMN and smaller units called Gemin proteins. In a normally functioning system, the SMN1 gene codes for SMN proteins that are part of the SMN complex that forms small nuclear ribonucleoproteins (snRNPs) from SM proteins and sRNA. The SMN protein binds to Gemin‐2 which holds five of the seven SM proteins, smaller units in snRNPs, in place until the target snRNA sequence is located. The final SM proteins are added when the N‐terminus of Gemin‐2 is moved. The snRNPs have many functions in cells, and five of them are involved in RNA splicing. Knowledge available on normal interactions of SMN and Gemin‐2 allow modeling of these proteins to be completed through 3D printing by the Hartford Union SMART (Students Modeling a Research Topic) Team. In children with SMA, the SMN protein cannot to bind to Gemin‐2 because Asp44 is replaced by valine, causing a break in the ionic bond holding the helices together. While this situation still produces normally operating snRNPs, there are too few to correctly splice the pre‐mRNA, leading to SMA. Grant Funding Source: Supported by a grant from NIH‐CTSA.

The average person's eyes adapt to darkness within minutes. For those with Oguchi's disease, adaptation can be slowed to several hours. Oguchi disease is an autosomal recessive disorder that results in greatly slowed phototransduction. Phototransduction is a cascade reaction beginning with a photon activating rhodopsin in the rod and leading to hyperpolarization of the cell. Oguchi disease is caused by mutations in rhodopsin kinase which prevent the phosphorylation of rhodopsin, lowering rhodopsin's affinity for arrestin. This reduced ability to bind arrestin decreases the speed in which rhodopsin is deactivated and prepped to reactivate. After a long period in a dark environment, the rhodopsin is eventually deactivated by arrestin, allowing it to be recycled. The Hartford Union High School SMART (Students Modelling a Research Topic) Team has designed a model of rhodopsin kinase to investigate its structure‐function relationship. Oguchi disease can be caused by two different mutations in rhodopsin kinase: large deletion or point mutation. In our 3D model, we will highlight the complete deletion of exon five, the partial deletion at the C‐terminus, and point mutations in the catalytic domain (Val380Asp and Pro391His) that cause Oguchi disease. Understanding the structure‐function relationships of rhodopsin kinase could shed more light on night blindness. This program is supported by a grant from NIH and CTSA.