Biology subjects

Syrjanen, J. L.

Publications and source records attributed to Syrjanen, J. L..

3 recordsLinked to original sources

bioRxiv2025

Structural insights into mechanisms of zinc scavenging by the Candida albicans zincophore Pra1

Candida albicans causes more than 400,000 life-threatening, and half a billion mucosal infections annually. In response to infection, the host limits availability of essential micronutrients, including zinc, to restrict growth of the invading pathogen. As assimilation of zinc is essential for C. albicans pathogenicity, its limitation induces the secretion of the zincophore protein Pra1 to scavenge zinc from the host. Pra1 also plays a number of important roles in host-pathogen interactions and is conserved in most fungi. However, the structure of fungal zincophores is not known. Here, we present the first cryogenic electron microscopy structures of C. albicans Pra1 in its apo- and zinc- bound states, at 2.8 and 2.5 [A] resolution respectively. Our work reveals a hexameric ring-like assembly with multiple zinc binding sites. Through genetic studies, we show that one of these zinc binding sites is essential for C. albicans growth under zinc restriction but does not affect the inflammatory properties of Pra1. These data provide a foundation for future work to explore the structural basis of Pra1-mediated host-pathogen interactions, C. albicans zinc uptake, as well therapeutics development.

biochemistry↗

bioRxiv2019

The Cryo-EM Structure of a Pannexin 1 Channel Reveals an Extracellular Gating Mechanism

Pannexins are large-pore forming channels responsible for ATP release under a variety of physiological and pathological conditions. Although predicted to share similar membrane topology with other large-pore forming proteins such as connexins, innexins, and LRRC8, pannexins have minimal sequence similarity to these protein families. Here, we present the cryo-EM structure of a pannexin 1 (Panx1) channel at 3.0 [A]. We find that Panx1 protomers harbor four transmembrane helices similar in arrangement to other large-pore forming proteins but assemble as a heptameric channel with a unique gate formed by Trp74 in the extracellular loop. Mutating Trp74 or the nearby Arg75 disrupt ion selectivity whereas altering residues in the hydrophobic groove formed by the two extracellular loops abrogates channel inhibition by carbenoxolone. Our structural and functional study establishes the extracellular loops as the unique structural determinants for channel gating and inhibition in Panx1 thereby providing the founding model to study pannexins.

neuroscience↗

bioRxiv2019

Structure and assembly of calcium homeostasis modulator proteins

Biological membranes of many tissues and organs contain large-pore channels designed to permeate a wide variety of ions and metabolites. Examples include connexin, innexin, and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), which permeate ions and ATP in a voltage-dependent manner to control neuronal excitability, taste signaling, and pathologies of depression and Alzheimers disease. Despite such critical biological roles, the structures and patterns of oligomeric assembly remain unclear. Here, we reveal the first structures of two CALHMs, CALHM1 and CALHM2, by single particle cryo-electron microscopy, which show novel assembly of the four transmembrane helices into channels of 8-mers and 11-mers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore-size, lipid accommodation, and channel activity.

biophysics↗