Efficient targeting of membrane proteins from the endoplasmic reticulum (ER) to the inner nuclear membrane depends on GTP hydrolysis by Atlastin GTPases and their function in maintaining an interconnected topology of the ER network.
Synthetic single domain antibody libraries and a binder selection cascade encompassing ribosome and phage display enable the selection of conformation-specific binders against previously intractable membrane proteins within three weeks.
Bioinformatics and experimental approaches identify families of membrane proteins requiring the co-ordinated action of the Sec pathway and Tat pathways for their integration and define features of the polypeptides that mediate interaction with these pathways.
Key sequence motifs, defined using the first reported structure of a monotopic membrane protein with a reentrant helix, enable identification of new monotopic membrane protein families previously predicted as membrane spanning.
Coarse-grained modeling reveals a new mechanism for multispanning membrane protein topogenesis, in which misintegrated configurations of the proteins undergo post-translational annealing to reach final, fully integrated multispanning topologies.