Biology subjects

Case, B.

Publications and source records attributed to Case, B..

2 recordsLinked to original sources

bioRxiv2021

Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail

The SARS-CoV-2 pandemic has led to an urgent need to understand the molecular basis for immune recognition of SARS-CoV-2 spike (S) glycoprotein antigenic sites. To define the genetic and structural basis for SARS-CoV-2 neutralization, we determined the structures of two human monoclonal antibodies COV2-2196 and COV2-21301, which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor binding domain (RBD) of SARS-CoV-2. COV2-2196 forms an "aromatic cage" at the heavy/light chain interface using germline-encoded residues in complementarity determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals1-4. The structure of COV2-2130 reveals that an unusually long LCDR1 and HCDR3 make interactions with the opposite face of the RBD from that of COV2-2196. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the critical residues of both antibodies and identified positions of concern for possible viral escape. Nonetheless, both COV2-2196 and COV2-2130 showed strong neutralizing activity against SARS-CoV-2 strain with recent variations of concern including E484K, N501Y, and D614G substitutions. These studies reveal germline-encoded antibody features enabling recognition of the RBD and demonstrate the activity of a cocktail like AZD7442 in preventing escape from emerging variant viruses.

immunology↗

bioRxiv2017

Spring frost controls spring tree phenology along elevational gradients on the southeastern Tibetan Plateau

Temperature is considered to be a main driver of spring phenology, whereas the role of climate extremes (such as spring frosts) has long been neglected. A large elevational gradient of mature forests on the Tibetan Plateau provides a powerful space-for-time natural experiment to explore driving forces of spring phenology. Combining 5-yr of in situ phenological observations of Smith fir (Abies georgei var. smithii) with concurrent air temperature data along two altitudinal gradients on the southeastern Tibetan Plateau, we tested the hypothesis that spring frost was a major factor regulating the timing of spring phenology. Onset of bud swelling and leaf unfolding in the study years occurred {approx} 18 or 17 days earlier, respectively, at the lowest (3800 m a.s.l.) elevation relative to upper treelines (4360 or 4380 m a.s.l.). The frequency of freezing events and last freezing date were critical factors in determining the timing of bud swelling along two altitudinal gradients, whereas onset of leaf unfolding was primarily controlled by the onset of bud swelling. This finding provides evidence for detrimental impacts of spring frost on spring phenology, which have been underappreciated in research on phenological sensitivity to climate but should be included in phenology models. It contributes to explain the declining global warming effects on spring phenophases, because climatic extreme events (e.g. spring frosts) tend to increase with warming.

ecology↗