From Protein Structure to Function with Bioinformatics.pdf

92 T. Nugent and D.T. Jones4.2 Structural Classes4.2.1 Alpha-Helical BundlesMembrane proteins can be classified into two basic types: alpha-helical and betabarrelproteins. Alpha-helical membrane proteins form the major category of TMproteins and are present in all type of biological membranes including bacterialouter membranes. They consist of one or more alpha helices, each of which containsa stretch of hydrophobic amino acids, is embedded in the membrane and islinked to any subsequent helices by extramembranous loop regions. It is thoughtsuch proteins may have up to 20 TM helices allowing a wide range of differingtopologies. Loop regions are known to contain substructures including re-entrantloops – short alpha helices that enter and exit the membrane on the same side – aswell as amphipathic helices that lie parallel to the membrane plane and globulardomains.Alpha-helical TM proteins can be further divided into a number of subtypes.Type I proteins have a single TM alpha helix, with the amino terminus exposed tothe exterior side of the membrane and the carboxy terminus exposed to the cytoplasmicside. These proteins are subdivided into two types. Type Ia – which constitutemost eukaryotic membrane proteins – contain cleavable signal sequences,while type Ib do not. Type II membrane proteins are similar to type I in that theyspan the membrane only once but their orientation is reversed; they have theiramino terminus on the cytoplasmic side of the cell and the carboxy terminus on theexterior.Type III membrane proteins have multiple TM helices in a single polypeptidechain and are also subdivided into types a and b: type IIIa have cleavable signalsequences while type IIIb have their amino termini exposed on the exterior surfaceof the membrane, but do not have cleavable signal sequences. Type III membraneproteins include the G-protein-coupled receptors (GPCR) family, members ofwhich consist of seven transmembrane helices (Fig. 4.1). GPCRs comprise a largeprotein family of receptors that sense molecules outside the cell, activate signaltransduction pathways and ultimately invoke cellular responses.Type IV membrane proteins have multiple domains which form an assembly thatspans the membrane multiple times. Domains may reside on a single polypeptidechain but are often composed of more than one. Examples include PhotosystemI which is comprised of nine unique chains (PDB code 1jb0).4.2.2 Beta-BarrelsBeta-barrel TM proteins have been found in outer membranes of Gram-negativebacteria, cell walls of Gram-positive bacteria, and the outer membranes of mitochondriaand chloroplasts. They consist of a series of anti-parallel beta strands