BackgroundPathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized.MethodsA survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated.ResultsStudent satisfaction with the lecture-based curriculum positively correlated with student grades (spearman’s correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman’s correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods.ConclusionsThe data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.
Crystal structures of transporters with a LeuT-type structural fold assign core transmembrane domain 6 (TM6') a central role in substrate binding and translocation. Here, the function of TM6' in the sodium/proline symporter PutP, a member of the solute/sodium symporter family, was investigated. A complete scan of TM6' identified eight amino acids as particularly important for PutP function. Of these residues, Tyr-248, His-253, and Arg-257 impact sodium binding, whereas Arg-257 and Ala-260 may participate in interactions leading to closure of the inner gate. Furthermore, the previous suggestion of an involvement of Trp-244, Tyr-248, and Pro-252 in proline binding is further supported. In addition, substitution of Gly-245, Gly-247, and Gly-250 affects the amount of PutP in the membrane. A Cys accessibility analysis suggests an involvement of the inner half of TM6' in the formation of a hydrophilic pathway that is open to the inside in the absence of ligands and closed in the presence of sodium and proline. In conclusion, the results demonstrate that TM6' plays a central role in substrate binding and release on the inner side of the membrane also in PutP and extend the knowledge on functionally relevant amino acids in transporters with a LeuT-type structural fold.
Import of preproteins into chloroplasts is an essential process, requiring two major multisubunit protein complexes that are embedded in the outer and inner chloroplast envelope membrane. Both the translocon of the outer chloroplast membrane (Toc), as well as the translocon of the inner chloroplast membrane (Tic) have been studied intensively with respect to their individual subunit compositions, functions and regulations. Recent advances in crystallography have increased our understanding of the operation of these proteins in terms of their interactions and regulation by conformational switching. Several subdomains of components of the Toc translocon have been studied at the structural level, among them the polypeptide transport-associated (POTRA) domain of the channel protein Toc75 and the GTPase domain of Toc34. In this review, we summarize and discuss the insight that has been gained from these structural analyses. In addition, we present the crystal structure of the Toc64 tetratrico-peptide repeat (TPR) domain in complex with the C-terminal domains of the heat-shock proteins (Hsp) Hsp90 and Hsp70.
The available structural information on LeuT and structurally related transporters suggests that external loop 4 (eL4) and the outer end of transmembrane domain (TM) 10 participate in the reversible occlusion of the outer pathway to the solute binding sites. Here, the functional significance of eL4 and the outer region of TM10 are explored using the sodium/proline symporter PutP as a model. Glu-311 at the tip of eL4, and various amino acids around the outer end of TM10 are identified as particularly crucial for function. Substitutions at these sites inhibit the transport cycle, and affect in part ligand binding. In addition, changes at selected sites induce a global structural alteration in the direction of an outward-open conformation. It is suggested that interactions between the tip of eL4 and the peptide backbone at the end of TM10 participate in coordinating conformational alterations underlying the alternating access mechanism of transport. Together with the structural information on LeuT-like transporters, the results further specify the idea that common design and functional principles are maintained across different transport families.
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