integraltransmembrane

Integral transmembrane proteins are a class of integral membrane proteins permanently embedded in the lipid bilayer, spanning it with one or more hydrophobic transmembrane segments. They are distinguished from peripheral membrane proteins, which associate with the membrane surface without fully crossing the bilayer. Transmembrane segments are commonly α-helical in eukaryotes and many bacteria, typically about 20–25 amino acids long, though some outer-m membrane proteins form β-barrels that traverse the membrane.

Topology and orientation are determined by the organization of transmembrane helices and by signal sequences that guide insertion. The positive-inside rule describes a tendency for cytoplasmic sides to contain more positively charged residues, influencing which domains face the cytosol versus the extracellular or periplasmic space. The arrangement of helices and loops gives each protein its specific geometry and function.

Functions of integral transmembrane proteins are diverse. They include receptors that detect environmental cues, channels and transporters that regulate ion and solute movement, enzymes that catalyze membrane-associated reactions, and anchors that organize cellular architecture. They play central roles in signaling, nutrient uptake, ion homeostasis, and cell communication, and many participate in adhesion processes.

Biogenesis and structure involve synthesis on cytosolic ribosomes with co-translational insertion through the translocon complexes (such as Sec61 in eukaryotes or SecYEG in bacteria). Folding, assembly, and post-translational modifications, like glycosylation of extracellular loops, contribute to stability and function.

Examples span a wide range, including G protein-coupled receptors (seven transmembrane helices), voltage-gated ion channels, transporters (such as glucose transporters), and aquaporins. Because of their accessibility and functional importance, integral transmembrane proteins are major targets in pharmacology.