RT Journal Article SR Electronic T1 Integrative model to coordinate the oligomerization and aggregation mechanisms of CCL5 JF bioRxiv FD Cold Spring Harbor Laboratory SP 755322 DO 10.1101/755322 A1 Yi-Chen Chen A1 Siou-Pei Chen A1 Jin-Ye Li A1 Pei-Chun Chen A1 Yi-Zong Lee A1 Kun-Mou Li A1 Raz Zarivach A1 Yuh-Ju Sun A1 Shih-Che Sue YR 2019 UL http://biorxiv.org/content/early/2019/09/03/755322.abstract AB The CC-type chemokine ligand 5 (CCL5) is involved in the pathogenesis of many inflammatory conditions. The oligomerization and aggregation of CCL5 are considered to be responsible for its inflammatory properties. The CC-type dimer acts as the basic unit to constitute the oligomer. However, the structural basis of CCL5 oligomerization remains controversial. In this study, NMR and biophysical analyses proposed evidence that no single dimer-dimer interaction dominates in the oligomerization process of CCL5. CCL5 could oligomerize alternatively through two different interactions, E66-K25 and E66-R44/K45. In addition, a newly determined trimer structure reported an interfacial interaction through the N-terminal 12FAY14 sequence. The interaction contributes to aggregation and precipitation. In accordance with the observations, an integrative model explains the CCL5 oligomerization and aggregation process. CCL5 assembly consists of two types of dimer-dimer interactions and one aggregation mechanism. For full-length CCL5, the molecular accumulation triggers oligomerization through the E66-K25 interaction, and the 12FAY14 interaction acts as a secondary effect to derive aggregation. The E66-R44/K45 interaction dominates in CCL5 N-terminal truncations. The interaction would lead to filament-like formation in solution.