BibTex format
@article{Lau:2026:10.1073/pnas.2520164123,
author = {Lau, R and Giblin, S and Sugar, A and Di, Maio A and Tassinie, G and Huse, K and Chorev, D and Chen, Y and Wu, G and Berg, Huemer C and Seung, YK and Matthewsa, J and Muloud, B and Chen, L and McKenna, S and Xu, Y and Massai, L and Muzzie, C and Ferhatie, X and Necchie, F and Gomes, Moriel D and Feizi, T and James, P and Sriskandan, S and Matthews, S},
doi = {10.1073/pnas.2520164123},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
title = {SpyCEP dismantles neutrophil immunity via disorder-driven chemokine remodeling and GAG targeting},
url = {http://dx.doi.org/10.1073/pnas.2520164123},
volume = {123},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Streptococcus pyogenes evades neutrophil-mediated immunity by secreting the protease SpyCEP, which inactivates chemokines such as CXCL8; however, the mechanism by which SpyCEP targets CXCL8 for cleavage has remained unclear. This work uncovers an intrinsically disordered autocatalytic maturation loop that binds CXCL8 and induces a conformationally heterogeneous state in the chemokine. A model is proposed in which this disorder-mediated recognition facilitates access to the substrate cleavage site and is compatible with SpyCEP acting at glycosaminoglycan (GAG)-bound CXCL8 reservoirs. This disorder-mediated mode of substrate recognition departs from classical protease–substrate interfaces and identifies the SpyCEP cleaved autocatalytic matu-ration loop (CAML) as a potential target for anti-virulence strategies against S. pyogenes.
AU - Lau,R
AU - Giblin,S
AU - Sugar,A
AU - Di,Maio A
AU - Tassinie,G
AU - Huse,K
AU - Chorev,D
AU - Chen,Y
AU - Wu,G
AU - Berg,Huemer C
AU - Seung,YK
AU - Matthewsa,J
AU - Muloud,B
AU - Chen,L
AU - McKenna,S
AU - Xu,Y
AU - Massai,L
AU - Muzzie,C
AU - Ferhatie,X
AU - Necchie,F
AU - Gomes,Moriel D
AU - Feizi,T
AU - James,P
AU - Sriskandan,S
AU - Matthews,S
DO - 10.1073/pnas.2520164123
PY - 2026///
SN - 0027-8424
TI - SpyCEP dismantles neutrophil immunity via disorder-driven chemokine remodeling and GAG targeting
T2 - Proceedings of the National Academy of Sciences of the United States of America
UR - http://dx.doi.org/10.1073/pnas.2520164123
VL - 123
ER -