The protein organization of a red blood cell

Red blood cells (RBCs) (erythrocytes) are the simplest primary human cells, lacking nuclei and major organ-elles and instead employing about a thousand proteins to dynamically control cellular function and morphology in response to physiological cues. In this study, we define a canonical RBC proteome and inter-actome using quantitative mass spectrometry and machine learning. Our data reveal an RBC interactome dominated by protein homeostasis, redox biology, cytoskeletal dynamics, and carbon metabolism. We vali-date protein complexes through electron microscopy and chemical crosslinking and, with these data, build 3D structural models of the ankyrin/Band 3/Band 4.2 complex that bridges the spectrin cytoskeleton to the RBC membrane. The model suggests spring-like compression of ankyrin may contribute to the characteristic RBC cell shape and flexibility. Taken together, our study provides an in-depth view of the global protein or-ganization of human RBCs and serves as a comprehensive resource for future research.

Automated summary

This study reveals the proteome and interactome of red blood cells using quantitative mass spectrometry and machine learning, and builds structural models of protein complexes. It provides a comprehensive resource for future research.