PT  - JOURNAL ARTICLE
AU  - Cherie S. Hesgrove
AU  - Kenny H. Nguyen
AU  - Sourav Biswas
AU  - Charles A. Childs
AU  - KC Shraddha
AU  - Bryan X. Medina
AU  - Vladimir Alvarado
AU  - Shahar Sukenik
AU  - Feng Yu
AU  - Marco Malferrari
AU  - Francesco Francia
AU  - Giovanni Venturoli
AU  - Erik W. Martin
AU  - Alex S. Holehouse
AU  - Thomas C. Boothby
TI  - Molecular Swiss Army Knives: Tardigrade CAHS Proteins Mediate Desiccation Tolerance Through Multiple Mechanisms
AID  - 10.1101/2021.08.16.456555
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.16.456555
4099  - http://biorxiv.org/content/early/2021/08/17/2021.08.16.456555.short
4100  - http://biorxiv.org/content/early/2021/08/17/2021.08.16.456555.full
AB  - Tardigrades, also known as water bears, make up a phylum of small but extremely robust animals renowned for their ability to survive extreme stresses including desiccation. How tardigrades survive desiccation is one of the enduring mysteries of animal physiology. Here we show that CAHS D, an intrinsically disordered protein belonging to a unique family of proteins possessed only by tardigrades, undergoes a liquid-to-gel phase transition in a concentration dependent manner. Unlike other gelling proteins such as gelatin, our data support a mechanism in which gelation of CAHS D is driven by intermolecular beta-beta interactions. We find that gelation of CAHS D promotes the slowing of diffusion, and coordination of residual water. Slowed diffusion and increased water coordination correlate with the ability of CAHS D to provide robust stabilization of an enzyme, lactate dehydrogenase, which otherwise unfolds when dried. Conversely, slowed diffusion and water coordination do not promote the prevention of protein aggregation during drying. Our study demonstrates that distinct mechanisms are required for holistic protection during desiccation, and that protectants, such as CAHS D, can act as ‘molecular swiss army knives’ capable of providing protection through several different mechanisms simultaneously.Competing Interest StatementThe authors have declared no competing interest.