An Introduction to the Steroidogenic Acute Regulatory Protein (StAR)-Related Lipid Transfer Domain Protein Family

Abstract

The steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain superfamily comprises a diverse group of proteins that bind hydrophobic lipids. The distinguishing feature shared by all members of this family is an α/β helix-grip fold structure containing a long hydrophobic pocket for ligand binding. The mammalian START domain protein family is grouped into 6 subfamilies that bind either cholesterol and oxysterols (STARD1/D3 and STARD4 subfamilies) or phospholipids and sphingolipids (STARD2/D11 subfamily), or have putative functions in Rho-GTPase signaling (STARD8/12/13 subfamily), thioesterase activity (STARD14/15 subfamily), or kinesin motor activity (STARD9). StAR (STARD1) is the namesake of the START domain protein family and has a well-established function in cholesterol transport in the adrenal and gonads for steroid hormone biosynthesis. Some of the mammalian START family members, e.g., STARD1, STARD11, and STARD2 are well characterized for their roles in cholesterol, ceramide, and phosphatidylcholine transfer, respectively, while much remains to be learned about the remaining family members. The purpose of this book is to present a compendium of the history of the discovery and the characterization of the mammalian START proteins, encompassing the seminal work over the past 50 years that has led to our current understanding of these lipid transport proteins. The chapters in this book focus on members of the STARD1/3 and STARD4 subfamilies, which have established roles involved in cholesterol and sterol trafficking. Each chapter provides a personal perspective of the discovery-to-publication journey for work on a START domain family member by authors whose work was instrumental in their discovery and characterization. This introductory chapter provides a brief overview and background on all members of the mammalian START protein family to provide a complete picture of this family of lipid transport proteins.