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Strategies to improve scFvs as crystallization chaperones suggested by analysis of a complex with the human PHD-bromodomain SP140

Fairhead, M.; Preger, C.; Wigren, E.; Strain-Damerell, C.; Ossipova, E.; Ye, M.; Makola, M.; Burgess-Brown, N. A.; Persson, H.; von Delft, F.; Graslund, S.

2019-09-13 biochemistry
10.1101/767376 bioRxiv
Show abstract

Antibody fragments have great potential as crystallization chaperones for structural biology due to their ability to either stabilise targets, trap certain conformations and/or promote crystal packing. Here we present an example of using a single-chain variable fragment (scFv) to determine the previously unsolved structure of the multidomain protein SP140. This nuclear leukocyte-specific protein contains domains related to chromatin-mediated gene expression and has been implicated in various disease states. The structure of two of the domains (PHD-bromodomain) was solved by crystallizing them as a complex with a scFv generated by phage display technology. SP140 maintains a similar overall fold to previous PHD-bromodomains and the scFv CDR loops predominately interact with the PHD, while the framework regions of the scFv makes numerous interactions with the bromodomain. Analysis of our and other complex structures suggest various protein engineering strategies that might be employed to improve the usefulness of scFvs as crystallization chaperones.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.