Making males in a fruit fly pest: The Mediterranean fruit fly or Medfly ( Ceratitis capitata ) is a global and highly destructive fruit pest. Meccariello et al. identified the master gene for male sex determination on the Y chromosome of Medfly and named it Maleness-on-the-Y ( MoY ) (see the Perspective by Makki and Meller). Flies of each sex were transformed into the other sex by genetic manipulation, and crosses of transformed files generated male and female progeny. MoY is functionally conserved in the olive fruit fly and in the invasive oriental fruit fly. This discovery has potential for insect genetic control based on mass release of sterile males and future strategies based on gene drive. Science , this issue p. 1457 ; see also p. 1380

Cullin 3 (Cul3) recognition by BTB domains is a key process in protein ubiquitination. Among Cul3 binders, a great attention is currently devoted to KCTD proteins, which are implicated in fundamental biological processes. On the basis of the high similarity of BTB domains of these proteins, it has been suggested that the ability to bind Cul3 could be a general property among all KCTDs. In order to gain new insights into KCTD functionality, we here evaluated and/or quantified the binding of Cul3 to the BTB of KCTD proteins, which are known to be involved either in cullin-independent (KCTD12 and KCTD15) or in cullin-mediated (KCTD6 and KCTD11) activities. Our data indicate that KCTD6^BTB and KCTD11^BTB bind Cul3 with high affinity forming stable complexes with 4:4 stoichiometries. Conversely, KCTD12^BTB and KCTD15^BTB do not interact with Cul3, despite the high level of sequence identity with the BTB domains of cullin binding KCTDs. Intriguingly, comparative sequence analyses indicate that the capability of KCTD proteins to recognize Cul3 has been lost more than once in distinct events along the evolution. Present findings also provide interesting clues on the structural determinants of Cul3-KCTD recognition. Indeed, the characterization of a chimeric variant of KCTD11 demonstrates that the swapping of α2β3 loop between KCTD11^BTB and KCTD12^BTB is sufficient to abolish the ability of KCTD11^BTB to bind Cul3. Finally, present findings, along with previous literature data, provide a virtually complete coverage of Cul3 binding ability of the members of the entire KCTD family.

Thrombin is the key enzyme of the entire hemostatic process since it is able to exert both procoagulant and anticoagulant functions; therefore, it represents an attractive target for the developments of biomolecules with therapeutic potential. Thrombin can perform its many functional activities because of its ability to recognize a wide variety of substrates, inhibitors, and cofactors. These molecules frequently are bound to positively charged regions on the surface of protein called exosites. In this review, we carried out extensive analyses of the structural determinants of thrombin partnerships by surveying literature data as well as the structural content of the Protein Data Bank (PDB). In particular, we used the information collected on functional, natural, and synthetic molecular ligands to define the anatomy of the exosites and to quantify the interface area between thrombin and exosite ligands. In this framework, we reviewed in detail the specificity of thrombin binding to aptamers, a class of compounds with intriguing pharmaceutical properties. Although these compounds anchor to protein using conservative patterns on its surface, the present analysis highlights some interesting peculiarities. Moreover, the impact of thrombin binding aptamers in the elucidation of the cross-talk between the two distant exosites is illustrated. Collectively, the data and the work here reviewed may provide insights into the design of novel thrombin inhibitors.

The discovery that the polypeptide chain has a remarkable and intrinsic propensity to form amyloid-like aggregates endowed with an extraordinary stability is one of the most relevant breakthroughs of the last decades in both protein/peptide chemistry and structural biology. This observation has fundamental implications, as the formation of these assemblies is systematically associated with the insurgence of severe neurodegenerative diseases. Although the ability of proteins to form aggregates rich in cross-β structure has been highlighted by recent studies of structural biology, the determination of the underlying atomic models has required immense efforts and inventiveness. Interestingly, the progressive molecular and structural characterization of these assemblies has opened new perspectives in apparently unrelated fields. Indeed, the self-assembling through the cross-β structure has been exploited to generate innovative biomaterials endowed with promising mechanical and spectroscopic properties. Therefore, this structural motif has become the fil rouge connecting these diversified research areas. In the present review, we report a chronological recapitulation, also performing a survey of the structural content of the Protein Data Bank, of the milestones achieved over the years in the characterization of cross-β assemblies involved in the insurgence of neurodegenerative diseases. A particular emphasis is given to the very recent successful elucidation of amyloid-like aggregates characterized by remarkable molecular and structural complexities. We also review the state of the art of the structural characterization of cross-β based biomaterials by highlighting the benefits of the osmosis of information between these two research areas. Finally, we underline the new promising perspectives that recent successful characterizations of disease-related amyloid-like assemblies can open in the biomaterial field.