Functional diversity and molecular interactions of small membrane proteins in bacteria

Bacteria constantly adapt to changing environmental conditions through diverse processes that involve numerous regulator and effector proteins. In this regard, small proteins play a significant role in promoting stress adaptation in bacteria. Although they were largely overlooked in early genome annotations, recent technological advances and a growing recognition of their significance have paved the way for the increasing identification and characterization of this intriguing class of proteins. Many small proteins contain a transmembrane domain and are integral to the cytoplasmic membrane. Others interact with and modulate membrane protein complexes. In this review, we focus on the current knowledge of these small membrane proteins, with an emphasis on their interactions, membrane insertion pathways, and toxicity.