Deep learning for protein interactions The use of deep learning has revolutionized the field of protein modeling. Humphreys et al . combined this approach with proteome-wide, coevolution-guided protein interaction identification to conduct a large-scale screen of protein-protein interactions in yeast (see the Perspective by Pereira and Schwede). The authors generated predicted interactions and accurate structures for complexes spanning key biological processes in Saccharomyces cerevisiae . The complexes include larger protein assemblies such as trimers, tetramers, and pentamers and provide insights into biological function. —VV

No abstract

Big molecules build small Actinomycete bacteria are prolific producers of bioactive small molecules such as polyketide antibiotics. These molecules are built by the addition of short carbon units to a growing, protein-tethered chain, either iteratively as in fatty acid synthesis or in a modular fashion by a hand-off from one distinct enzyme complex to the next. Bagde et al . and Cogan et al . report structures of polyketide synthase modules in action, taking advantage of antibody stabilization of one of the domains. Both groups visualized multiple conformational states and an asymmetric arrangement of domains, providing insight into how these molecular assembly machines transfer substrates from one active site to another. —MAF

Rab1 and Rab11 are essential regulators of the eukaryotic secretory and endocytic recycling pathways. The transport protein particle (TRAPP) complexes activate these guanosine triphosphatases via nucleotide exchange using a shared set of core subunits. The basal specificity of the TRAPP core is toward Rab1, yet the TRAPPII complex is specific for Rab11. A steric gating mechanism has been proposed to explain TRAPPII counterselection against Rab1. Here, we present cryo–electron microscopy structures of the 22-subunit TRAPPII complex from budding yeast, including a TRAPPII-Rab11 nucleotide exchange intermediate. The Trs130 subunit provides a “leg” that positions the active site distal to the membrane surface, and this leg is required for steric gating. The related TRAPPIII complex is unable to activate Rab11 because of a repulsive interaction, which TRAPPII surmounts using the Trs120 subunit as a “lid” to enclose the active site. TRAPPII also adopts an open conformation enabling Rab11 to access and exit from the active site chamber.