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Better together: building protein oligomers naturally and by design.

ABSTRACT: Protein oligomers are more common in nature than monomers, with dimers being the most prevalent final structural state observed in known structures. From a biological perspective, this makes sense as it conserves vital molecular resources that may be wasted simply by generating larger single polypeptide units, and allows new features such as cooperativity to emerge. Taking inspiration from nature, protein designers and engineers are now building artificial oligomeric complexes using a variety of approaches to generate new and useful supramolecular protein structures. Oligomerisation is thus offering a new approach to sample structure and function space not accessible through simply tinkering with monomeric proteins.

SUBMITTER: Gwyther REA

PROVIDER: S-EPMC6925524 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Better together: building protein oligomers naturally and by design.

Gwyther Rebecca E A REA Jones D Dafydd DD Worthy Harley L HL

Biochemical Society transactions 20191201 6

Protein oligomers are more common in nature than monomers, with dimers being the most prevalent final structural state observed in known structures. From a biological perspective, this makes sense as it conserves vital molecular resources that may be wasted simply by generating larger single polypeptide units, and allows new features such as cooperativity to emerge. Taking inspiration from nature, protein designers and engineers are now building artificial oligomeric complexes using a variety of ...[more]

PMID: 31803901

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Project description:PurposeEating disorders are prevalent public health problems associated with broad psychosocial impairments and with elevated rates of psychiatric and medical comorbidities. Critical reviews of the treatment literature for eating disorders indicate that although certain specialized psychological treatments and specific medications show efficacy to varying degrees across the different eating disorders, many patients fail to derive sufficient benefit from existing treatments. This article addresses whether combining psychological and pharmacologic interventions confers any additional benefits for treating eating disorders.MethodsThis study was a critical review of randomized controlled trials (RCTs) testing combined psychological and pharmacologic treatment approaches for eating disorders with a focus on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED).FindingsFor AN, 3 of the 4 RCTs reported no significant advantage for combining treatments; the fourth reported a statistically significant, albeit clinically modest, advantage. For BN, 10 of the 12 RCTs reported no significant advantage for combining treatments; 2 RCTs found that combining fluoxetine with specific psychological treatments enhanced outcomes relative to medication only but not relative to the psychological treatments only. For BED, of the 12 RCTs, only 2 (both with antiseizure medications) significantly enhanced both binge-eating and weight outcomes, and only 2 (with orlistat, a weight-loss medication) enhanced weight loss but not binge-eating outcomes.ImplicationsDespite the public health significance of eating disorders, the scope of research performed on the utility of combining treatments is limited. To date, the few RCTs testing combined pharmacologic plus psychological treatments for eating disorders have yielded mostly nonsignificant findings. Future RCTs should focus on testing additive benefits of medications with relevant mechanisms of action to available effective psychological interventions. In addition, future RCTs that test additive effects should use adaptive designs, which could inform treatment algorithms to enhance outcomes among both responders and nonresponders to initial interventions.

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Better together: building protein oligomers naturally and by design.

Publications

Better together: building protein oligomers naturally and by design.

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