Science - USA (2020-09-25)

PHOTO: NEIL BROMHALL/SHUTTERSTOCK

SCIENCE sciencemag.org

PROTEIN DESIGN

Logic at the cell surface

A major challenge in medical

interventions is to target only

diseased cells. Although there

are biomarkers characteristic of

certain cancers, for example, it

is unlikely that a single marker

can specify a particular cell type.

Lajoie et al. addressed this prob-

lem by designing protein switches

called Co-LOCKR that bind to

antigens on the cell surface and

activate through a conformational

change only when there is a

precise combination of antigens.

They designed switches that can

perform AND, OR, and NOT logic.

On the path toward applying this

technology, they used Co-LOCKR

to direct chimeric antigen

receptor T cells to tumor cells

expressing specific antigens. —VV

Science, this issue p. 1637

CORONAVIRUS

A dynamic viral spike

Efforts to protect human cells

against severe acute respira-

tory syndrome coronavirus 2

(SARS-CoV-2) have focused on

the trimeric spike (S) protein.

Several structures have shown

a stabilized ectodomain of the

spike in its prefusion confor-

mation. Cai et al. now provide

insight into the structural

changes in the S protein that

result in the fusion of the viral

and host cell membranes. They

purified full-length S protein

and determined cryo–electron

microscopy structures of both

the prefusion and postfusion

conformations. These structures

add to our understanding of

S protein function and could

inform vaccine design. —VV

Science, this issue p. 1586

CORONAVIRUS

Modeling SARS-CoV-2

in mice

Among the research tools

necessary to develop medical

interventions to treat severe acute

respiratory syndrome coronavirus

2 (SARS-CoV-2) infections, high

on the list are informative animal

models with which to study viral

pathogenesis. Gu et al. devel-

oped a mouse model in which a

SARS-CoV-2 strain was infectious

and could cause an inflamma-

tory response and moderate

pneumonia. Adaptation of this

IN SCIENCE JOURNALS

Edited by Michael Funk

IMMUNE SYSTEMS

Reconfiguring an

immune response

T

he deep sea is a vast and

generally empty environ-

ment. Finding a mate can thus

be difficult. In response to this

situation, one group of deep-sea

denizens, the anglerfishes, have evolved

a system in which males attach to females,

in some cases permanently, through fusion of tis-

sues and connection of circulatory systems. Such

attachment greatly challenges the immune systems

of the fish. Swann et al. found that these challenges

have been met by the evolution of increasingly reduced

immune responses among anglerfish species, including

the loss of what have been considered essential verte-

brate responses. These shifts suggest that vertebrate

immune systems may be more flexible over evolution-

ary time than was previously thought. —SNV

Science, this issue p. 1608

A female anglerfish of the species Haplophryne mollis supports a dorsally

fused male fish, an arrangement requiring immune system changes.

RESEARCH

25 SEPTEMBER 2020 • VOL 369 ISSUE 6511 1579