Expanding the molecular language of protein liquid-liquid phase separation

序列(生物学) 残留物(化学) 肽序列 化学物理 化学 相(物质) 生物物理学 生物化学 生物 有机化学 基因
作者
Shiv Rekhi,Cristobal Garcia Garcia,Mayur Barai,Azamat Rizuan,Benjamin S. Schuster,Kristi L. Kiick,Jeetain Mittal
标识
DOI:10.1101/2023.03.02.530853
摘要

Abstract Understanding the relationship between an amino acid sequence and its phase separation has important implications for analyzing cellular function, treating disease, and designing novel biomaterials. Several sequence features have been identified as drivers for protein liquid-liquid phase separation (LLPS), leading to the development of a “molecular grammar” for LLPS. In this work, we further probed how sequence modulates phase separation and the material properties of the resulting condensates. Specifically, we used a model intrinsically disordered polypeptide composed of an 8-residue repeat unit and performed systematic sequence manipulations targeting sequence features previously overlooked in the literature. We generated sequences with no charged residues, high net charge, no glycine residues, or devoid of aromatic or arginine residues. We report that all but one of the twelve variants we designed undergo LLPS, albeit to different extents, despite significant differences in composition. These results support the hypothesis that multiple interactions between diverse residue pairs work in tandem to drive phase separation. Molecular simulations paint a picture of underlying molecular details involving various atomic interactions mediated by not just a handful of residue types, but by most residues. We characterized the changes to inter-residue contacts in all the sequence variants, thereby developing a more complete understanding of the contributions of sequence features such as net charge, hydrophobicity, and aromaticity to phase separation. Further, we find that all condensates formed behave like viscous fluids, despite large differences in their viscosities. The results presented in this study significantly advance the current sequence-phase behavior and sequence-material properties relationships to help interpret, model, and design protein assembly.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
weixiaozdw完成签到,获得积分10
刚刚
晨陌兮客发布了新的文献求助10
刚刚
心静如水发布了新的文献求助10
刚刚
小二郎应助科学细胞采纳,获得10
1秒前
陈谨完成签到 ,获得积分10
1秒前
297同学发布了新的文献求助10
1秒前
Devon完成签到,获得积分10
1秒前
1秒前
王秋田完成签到,获得积分10
1秒前
TianxingLiu完成签到,获得积分10
2秒前
SciGPT应助科研通管家采纳,获得10
2秒前
daisies应助科研通管家采纳,获得20
2秒前
yar应助科研通管家采纳,获得10
2秒前
华仔应助科研通管家采纳,获得10
2秒前
2秒前
2秒前
琉璃应助科研通管家采纳,获得10
3秒前
战战发布了新的文献求助10
3秒前
yar应助科研通管家采纳,获得10
3秒前
wy.he应助科研通管家采纳,获得10
3秒前
3秒前
wy.he应助科研通管家采纳,获得10
3秒前
3秒前
搜集达人应助科研通管家采纳,获得10
3秒前
3秒前
3秒前
3秒前
3秒前
3秒前
weixiaozdw发布了新的文献求助10
3秒前
科目三应助科研通管家采纳,获得10
3秒前
3秒前
3秒前
3秒前
3秒前
CodeCraft应助科研通管家采纳,获得10
4秒前
4秒前
4秒前
4秒前
JamesPei应助乌龟娟采纳,获得10
5秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970632
求助须知:如何正确求助?哪些是违规求助? 3515261
关于积分的说明 11177794
捐赠科研通 3250448
什么是DOI,文献DOI怎么找? 1795314
邀请新用户注册赠送积分活动 875781
科研通“疑难数据库(出版商)”最低求助积分说明 805073