Iron and bismuth bound human serum transferrin reveals a partially-opened conformation in the N-lobe

Human serum transferrin (hTF) binds Fe(III) tightly but reversibly, and delivers it to cells via a receptor-mediated endocytosis process. The metal-binding and release result in significant conformational changes of the protein. Here, we report the crystal structures of diferric-hTF (Fe N Fe C-hTF) and bismuth-bound hTF (Bi N Fe C-hTF) at 2.8 and 2.4 Å resolutions respectively. Notably, the N-lobes of both structures exhibit unique 'partially-opened' conformations between those of the apo-hTF and holo-hTF. Fe(III) and Bi(III) in the N-lobe coordinate to, besides anions, only two (Tyr95 and Tyr188) and one (Tyr188) tyrosine residues, respectively, in contrast to four residues in the holo-hTF. The C-lobe of both structures are fully closed with iron coordinating to four residues and a carbonate. The structures of hTF observed here represent key conformers captured in the dynamic nature of the transferrin family proteins and provide a structural basis for understanding the mechanism of metal uptake and release in transferrin families. © 2012 Macmillan Publishers Limited. All rights reserved.published_or_final_versio

Threshold concepts and certainty: a critical analysis of ‘troublesomeness’

The threshold concept framework is a key contemporary theory in pedagogy. The core idea is that ‘threshold concepts’ are distinctively ‘troublesome’ for students and act as gatekeepers to their disciplines. No doubt the theory is compelling because there is surely something right about this. Student difficulty with conceptual material is familiar to all teaching practitioners. Furthermore, to avoid rote levels of understanding, mastery of discipline-specific conceptual material is key. However, TCF has struggled to articulate key dimensions of its theory: it is without a methodology for identifying threshold concepts. It has also faltered in explaining how student difficulty is a function of difficulties endemic to the concepts, rather than as a contingent phenomenon about individual students. I offer a novel way to think about identifying threshold concepts, and for theorising student difficulties which may arise from those concepts. I argue that there is an ‘existential’ kind of certainty which acts as a framework within which epistemic activities take place. Disciplines which theorise concepts in ways that clash with students’ existential certainties are candidates for threshold concepts and may generate ‘objective’ difficulties for students. As much as I think theorising existential certainty helps TCF overcome theoretical challenges, it would require revisions to the way that it is currently being theorised and applied. I also believe that even without attachments to TCF, ‘existential certainty’ is a real phenomenon, shaping the very possibilities of student experience, and which any pedagogical theory should be aware of