Integrative Protein Physiology
connecting cellular pathways
The native conformation is determined by the totality of interatomic interactions and hence by the amino acid sequence, in a given environment.
Christian B. Anfinsen
What are proteins?
Proteins are bio-macromolecules that come in many shapes and forms. They can be viewed as molecular machines and are key players in metabolic processes, intracellular signaling and trafficking, cell-to-cell and long-range communication, among others. Proteins are synthesized as strings of amino acids that then need to fold into a three-dimensional structure to be functional. These structures are not static and one single protein, in many cases, can adopt different conformations, with different activities.
Membrane proteins
Membrane proteins, such as ion channels, transporters, or receptors, are embedded into cellular membranes where they establish a physical connection between both sides of the membrane. Like this, they take on central roles during intra-cellular signaling as well as cell-to-cell communication. Inserting these proteins into hydrophobic membranes comes with unique challenges and in cells specialized machineries have evolved for this task. We are facing very similar challenges when working with membrane proteins in the lab.
Proteins in context
In cells, proteins often form complexes with other proteins or ligands which can lead to the generation of large, multi-molecular signaling complexes. In this scenario, the function of individual proteins can be modulated by specific protein-protein interactions adding an extra level of complexity to protein physiology. It also allows to connect different cellular pathways via shared, participating proteins. We are just in the early stages of understanding the range of functions that can be achieved that way.
Lab synopsis
Every protein in a living organism works in the presence of many other proteins or other cellular components and protein-protein or protein-ligand interactions are commonly used to modulate protein function. Our research is geared towards understanding how membrane proteins physically interact with various, cellular pathways and how such interactions alter protein structure, function, and dynamics. Using omics approaches, we seek to identify so far unknown protein-protein interactions between signaling pathways. Once identified, these complexes will be reconstituted in vitro from purified components. This allows us to compare the activity of the purified protein alone to conditions with specific components added back. In a nutshell, our goal is to gain better understanding of the versatility of proteins beyond their established functions and to link different biological pathways on a molecular level. Ultimately, this will lead to a more integrative understanding of protein physiology and cellular networks.
Lab environment
Our lab is located in the Department of Chemistry within the College of Sciences at the University of Texas at San Antonio (UTSA). Established in 1969, UTSA has emerged as a leading research institution, enrolling almost 35,000 students from 90 countries. Notably, 69% of students are from underrepresented groups, and 45% are first-generation college students. We share the strong commitment of UTSA for student success and research excellence.
Our newly renovated lab space is fully equipped for protein expression in bacteria, yeast, insect cells, and mammalian cells. The lab features state-of-the-art instrumentation for molecular biology and protein biochemistry, including latest-generation Äkta systems for protein purification. For kinetic studies of protein folding and protein function, our lab has a sequential mixing stopped-flow fluorescence spectrophotometer, for single channel recordings of purified ion channels we have a four-channel Orbit mini.
Additionally, as part of the Department of Chemistry, we have access to a wide range of optical spectroscopy techniques, such as absorbance, fluorescence, and circular dichroism. In addition, expertise and instrumentation is available for NMR and EPR spectroscopy. The research cores at UTSA provide resources in mass spectrometry, advanced microscopy, and cell analysis. Cryo-EM access is available through UT Health at San Antonio as well as national centers.
Copyright © 2023 Philipp Schmidpeter