![]() ![]() ![]() PDB identifiers are given in parentheses. A single representative from each superfamily is shown colored by protein chain. MacB is therefore the “holotype” for the Type VII ABC transporter superfamily ( Crow et al., 2017), and the first structurally-characterized member of a clade of ABC transporters classified by Saier as the ABC3 superfamily ( Wang et al., 2009).įigure 1. Analysis of available ABC transporter crystal structures shows that there are at least seven structurally distinct ABC transporter folds, of which MacB is the most-recently determined representative (Figure 1). The NBDs at the core of all ABC transporters are homologous, while the TMDs are structurally heterogeneous and proposed to have discrete evolutionary origins ( Wang et al., 2009 ter Beek et al., 2014 Locher, 2016). All ABC transporters possess conserved nucleotide binding domains (NBDs) that facilitate power generation through ATP hydrolysis, and transmembrane domains (TMDs) that determine transporter function. ![]() In addition, many MacB-like ABC transporters do not form tripartite pumps, but instead operate in diverse cellular processes including antibiotic sensing, cell division and lipoprotein trafficking.ĪBC (ATP-binding cassette) transporters are present in all three domains of life, and mediate transmembrane transport of a diverse array of substrates including drugs, sugars, ions, amino acids and proteins ( ter Beek et al., 2014 Locher, 2016). Homologous tripartite systems from pathogenic bacteria similarly export protein-like signaling molecules, virulence factors and siderophores. In the MacAB-TolC tripartite pump, mechanotransmission drives efflux of antibiotics and export of a protein toxin from the periplasmic space via the TolC exit duct. Unlike other bacterial ABC transporters, MacB does not transport substrates across the inner membrane in which it is based, but instead couples cytoplasmic ATP hydrolysis with transmembrane conformational changes that are used to perform work in the extra-cytoplasmic space. MacB has a fold that is distinct from other structurally characterized ABC transporters and uses a unique molecular mechanism termed mechanotransmission. Here, we review recent structural and functional data on MacB and its homologs. The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria. 2School of Life Sciences, University of Warwick, Coventry, United Kingdom.1Department of Pathology, University of Cambridge, Cambridge, United Kingdom. ![]() Greene 1, Elise Kaplan 1, Allister Crow 2 and Vassilis Koronakis 1 * The median age at death (29 years) in XP patients with neurodegeneration was significantly younger than those XP patients without neurodegeneration (37 years) (p=0.02).Nicholas P. #Xeroderma pigmentosum pdf skinThe most common causes of death were skin cancer (34%, n=10), neurologic degeneration (31%, n=9), and internal cancer (17%, n=5). Progressive neurologic degeneration was present in 24% (n=25) with 16/25 in complementation group XP-D. This may be related to the extreme sun protection they receive from an earlier age, decreasing their total ultraviolet exposure. XP patients with pronounced burning on minimal sun exposure (n=65) were less likely to develop skin cancer than those who did not. The 9 year median age at diagnosis of first non-melanoma skin cancer (NMSC) (n=64) was significantly younger than the 22 year median age at diagnosis of first melanoma (n=38)-a relative age reversal from the general population suggesting different mechanisms of carcinogenesis between NMSC and melanoma. Results In the 65 per cent (n=69) of patients with skin cancer, non-melanoma skin cancer (NMSC) was increased 10 000-fold and melanoma was increased 2000-fold in patients under age 20. Correspondence to Dr Kenneth H Kraemer, DNA Repair Section, Dermatology Branch, Center for Cancer Research, National Cancer Institute, Building 37 Room 40, Bethesda, MD 20892-4258, USA.4Dermatology Department, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.3Laboratory of Molecular Technology, National Cancer Institute at Frederick, Science Applications International Corporation, Frederick, Maryland, USA.2Dermatology Branch, National Cancer Institute, Bethesda, Maryland, USA.1Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, USA. ![]()
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