The STI1-domain is a flexible alpha‐helical fold with a hydrophobic groove
STI1‐domains are present in a variety of co‐chaperone proteins and are required for the transfer of hydrophobic clients in various cellular processes. The domains were first identified in the yeast Sti1 protein where they were referred to as DP1 and DP2. Based on hidden Markov model searches, this domain had previously been found in other proteins including the mammalian co‐chaperone SGTA, the DNA damage response protein Rad23, and the chloroplast import protein Tic40. Here, we refine the domain definition and carry out structure‐based sequence alignment of STI1‐domains showing conservation of five amphipathic helices. Upon examinations of these identified domains, we identify a preceding helix 0 and unifying sequence properties, determine new molecular models, and recognize that STI1‐domains nearly always occur in pairs. The similarity at the sequence, structure, and molecular levels likely supports a unified functional role.
© 2021 The Protein Society. Issue Online: 20 March 2021; Version of Record online: 04 March 2021; Accepted manuscript online: 23 February 2021; Manuscript accepted: 18 February 2021; Manuscript revised: 17 February 2021; Manuscript received: 31 December 2020. Research funding: National Science Foundation Graduate Research. Grant Number: 1144469; National Research Service Award Training. Grant Number: T32 GM07616; National Institutes of Health. Grant Numbers: GM097572, GM105385.
Supplemental Material - pro4049-sup-0001-figures1.eps