Structure and function of an effector domain in antiviral factors and tumor suppressors SAMD9 and SAMD9L

Abstract

Significance SAMD9 and SAMD9L (SAMD9/9L) are important innate immune defenders against viruses and the development of myeloid tumors. They form a crucial host barrier that poxviruses must overcome for successful infection. A myriad of human diseases including many pediatric myelodysplastic syndromes are caused by mutations in SAMD9/9L. However, the molecular functions of SAMD9/9L and how their functions are executed are unknown, hindering progress in developing effective therapies for SAMD9/9L-associated human diseases. Here, we identified the structure and function of a SAMD9/9L effector domain that is essential for their physiological functions as well as the pathogenic effects exerted by patient-derived mutations. Our study revealed a potential therapeutic target for SAMD9/9L-associated human diseases.