ABSTRACT

Introduction

The proteins that decipher nucleic acid- and protein-based information are well known, however, those that read membrane-encoded information remain understudied. Here, we report 70 different human, microbial and viral protein folds that recognize phosphoinositides (PIs), comprising the readers of a vast membrane code.

Areas covered

Membrane recognition is best understood for FYVE, PH and PX domains, which exemplify hundreds of PI code readers. Comparable lipid interaction mechanisms may be mediated by kinases, adjacent C1 and C2 domains, trafficking arrestins, GAT and VHS modules, membrane-perturbing annexins, BAR, CHMP, ENTH, HEAT, syntaxin and Tubby helical bundles, multipurpose FERM, EH, MATH, PHD, PDZ, PROPPIN, PTB and SH2 domains, as well as systems that regulate receptors, GTPases and actin filaments, transfer lipids, and assemble bacterial and viral particles.

Expert opinion

The elucidation of how membranes are recognized has extended the genetic code to the PI code. Novel discoveries include PIP-stop and MET-stop residues to which phosphates and metabolites are attached to block phosphatidylinositol phosphate (PIP) recognition, memteins as functional membrane protein apparatuses and lipidons as lipid ‘codons’ recognized by membrane readers. At least 5% of the human proteome senses such membrane signals and allows eukaryotic organelles and pathogens to operate and replicate.

中文翻译：

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磷酸肌醇代码被大量蛋白质结构域读取

摘要

介绍

破译核酸和蛋白质信息的蛋白质是众所周知的，然而，那些读取膜编码信息的蛋白质仍未得到充分研究。在这里，我们报告了 70 种不同的人类、微生物和病毒蛋白质折叠，它们识别磷酸肌醇 (PI)，包括大量膜代码的读者。

涵盖的领域

FYVE、PH 和 PX 域最能理解膜识​​别，这些域是数百个 PI 代码阅读器的例证。类似的脂质相互作用机制可能由激酶、相邻的 C1 和 C2 结构域、转运抑制蛋白、GAT 和 VHS 模块、膜干扰膜联蛋白、BAR、CHMP、ENTH、HEAT、突触蛋白和 Tubby 螺旋束、多功能 FERM、EH、MATH、 PHD、PDZ、PROPPIN、PTB 和 SH2 结构域，以及调节受体、GTP 酶和肌动蛋白丝、转移脂质以及组装细菌和病毒颗粒的系统。

专家意见

对如何识别膜的阐明已将遗传密码扩展到 PI 密码。新发现包括 PIP-stop 和 MET-stop 残基，磷酸盐和代谢物附着在其上以阻断磷酸磷脂酰肌醇 (PIP) 识别，作为功能性膜蛋白装置的 memteins 和作为膜阅读器识别的脂质“密码子”的脂质体。至少 5% 的人类蛋白质组感知到这种膜信号，并允许真核细胞器和病原体进行操作和复制。