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Transmembrane Domain
Original
Transmembrane domain usually denotes a transmembrane segment of single alpha helix of a transmembrane protein.[1] More broadly, a transmembrane domain is any membrane-spanning protein domain.
Proposed additions below
Integral membrane proteins account for 20–30% of protein-coding genes and play critical roles in cellular functions such as signal transduction, molecular transport, and cell adhesion.[1] The transmembrane domain (TMD) is made up mostly of hydrophobic amino acids and spans the cellular or organelle membrane, generally adopting an alpha helix topological conformation.[2] TMDs vary greatly in length, sequence, and hydrophobicity, adopting organelle-specific properties.[1]
The Role of Membrane Protein Biogenesis and Quality Control Factors
Since protein translation is performed in the cytosol (i.e. an aqueous environment), factors that recognize the TMD and protect them in an inhospitable environment are required. Additional factors that allow the TMD to be incorporated into the target membrane (endoplasmic reticulum or other organelles) are also required.[1] Furthermore, factors identify TMD misfolding within the membrane and perform quality control functions. These factors must be able to recognize a highly variable set of TMDs and can be segregated into those active in the cytosol or active in the membrane.[1]
Cytosolic Recognition Factors
Broadly, cytosolic recognition factors can be thought to employ two different strategies.[1] In the co-translational strategy the the recognition and shielding are coupled to protein synthesis. Genome wide association studies indicate the majority of membrane proteins targeting the endoplasmic reticulum are handled by the signal recognition particle which is bound to the ribosomal exit tunnel and initiates recognition and shielding as protein is translated. The second strategy involves tail-anchored proteins, defined by a single TMD located close to the carboxyl terminus of the membrane protein. The tail-anchored TMD remains in the ribosomal exit tunnel once translation is terminated and an ATPase mediates targeting to the endoplasmic reticulum (e.g. TRC40 in higher eukaryotes and Get3 in yeast). Additionally, general TMD-binding factors serve to protect from aggregation or other disrupting interactions. Known general TMD-binding factors include SGTA and calmodulin. Quality control of membrane proteins involve TMD-binding factors that are linked to ubiquitination proteasome system.
Membrane Recognition Factors
Once transported, factors assist with insertion of the TMD across the hydrophilic layer phosphate "head" group of the phospholipid membrane.[1] Quality control factors must be able to discern function and topology, as well as facilitate transport back to the cytosol. The signal recognition particle delivers membrane proteins to the Sec translocation channel which positions the ribosome exit tunnel proximal to the translocon central pore and minimizes exposure of the TMD to cytosol.
- ^ a b c d e f g Guna, Alina; Hegde, Ramanujan S. (2018-04-23). "Transmembrane Domain Recognition during Membrane Protein Biogenesis and Quality Control". Current biology: CB. 28 (8): R498 – R511. doi:10.1016/j.cub.2018.02.004. ISSN 1879-0445. PMID 29689233.
- ^ Sharpe, Hayley J.; Stevens, Tim J.; Munro, Sean (2010-07-09). "A Comprehensive Comparison of Transmembrane Domains Reveals Organelle-Specific Properties". Cell. 142 (1): 158–169. doi:10.1016/j.cell.2010.05.037. ISSN 0092-8674. PMC 2928124. PMID 20603021.