Structural and functional insights from the sequences and complex domain architecture of adhesin-like proteins from and .

Methanogenic archaea, or methanogens, are crucial in guts and rumens, consuming hydrogen, carbon dioxide, and other fermentation products. While their molecular interactions with other microorganisms are not fully understood, genomic sequences provide information. The first genome sequences of human gut methanogens, and , revealed genes encoding adhesin-like proteins (ALPs). These proteins were also found in other gut and rumen methanogens, but their characteristics and functions remain largely unknown. This study analyzes the ALP repertoire of and using AI-guided protein structure predictions of unique ALP domains. Both genomes encode more than 40 ALPs each, comprising over 10% of their genomes. ALPs contain repetitive sequences, many of which are unmatched in protein domain databases. We present unique sequence signatures of conserved ABD repeats in ALPs and propose a classification based on domain architecture. Our study offers insights into ALP features and how methanogens may interact with other microorganisms.