Coupling Proteins in Type IV SecretionCoupling Proteins in Type IV SecretionMatxalen Llosa and Itziar Alkorta2018-03-13T23:00:00Z<p><strong>​</strong><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2"><strong>Abstract </strong></span></p><p style="margin-bottom:0px;font-stretch:normal;line-height:normal;text-align:justify;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">Type IV coupling proteins (T4CPs) are essential constituents of most type IV secretion systems (T4SSs), and probably the most intriguing component in terms of their evolutionary origin and functional role. Coupling proteins have coevolved with their cognate secretion system and translocated substrates. They are present in all conjugative systems, leading to the suggestion that they play a speci<span style="font-stretch:normal;line-height:normal;">fi</span>c role in DNA transfer. However, they are also part of many T4SSs involved in bacterial virulence, where they are required for protein translocation, with no apparent involvement in DNA secretion. Their name re<span style="font-stretch:normal;line-height:normal;">fl</span>ects genetic and biochemical evidence of a connecting role between the substrate and the T4SS, thus probably playing a major role in substrate recruitment. Increasing evidence supports also a role in signal transmission leading to activation of secretion. Most studies have addressed conjugative coupling proteins of the VirD4-like protein family.<br></span></p><p style="margin-bottom:0px;font-stretch:normal;line-height:normal;text-align:justify;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">Their conserved features include a nucleotide-binding domain, essential for substrate translocation, a C-terminal domain involved in substrate interactions, and a transmembrane domain anchoring them to the inner membrane, which is an important regulator of protein function. Puri<span style="font-stretch:normal;line-height:normal;">fi</span> ed soluble deletion mutants display ATP hydrolysis activity and unspeci<span style="font-stretch:normal;line-height:normal;">fi</span> c DNA binding. Elucidation of the 3D structure of the soluble deletion mutant of the conjugative coupling protein TrwB,</span></p><p style="margin-bottom:0px;font-stretch:normal;font-size:10px;line-height:normal;font-family:times;text-align:justify;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">TrwB</span><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2" style="font-stretch:normal;line-height:normal;">D</span><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2"> N70, provided the basis for further mutagenesis studies rendering interesting insights into the structure</span><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2" style="font-stretch:normal;line-height:normal;">–</span><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2"> function of these proteins. Their key role as couplers between substrate and transporter provides biotechnological potential as targets for anti-virulence strategies, as well as for customization of substrate delivery through heterologous secretion systems.</span><br></p><p><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">​</span></p><a href="https://www.ncbi.nlm.nih.gov/pubmed/29536358"><p style="margin-bottom:0px;font-stretch:normal;line-height:normal;"><span style="font-size:11pt;">Type IV Secretion in Gram-Negative and Gram-Positive Bacteria.Current Topics in Microbiology and Immunology 413, https://doi.org/10.1007/978-3-319-75241-9_6</span></p></a><p style="margin-bottom:0px;font-stretch:normal;line-height:normal;"></p>176