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

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Cholesterol Transporters of the START Domain Protein Family in Health and Disease

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.

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Notes

  1. 1.

    NCBI cl14643: SRPBCC is the START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC superfamily. Rho_alpha_C, the C-terminal catalytic domains of the alpha oxygenase subunit of Rieske-type non-heme iron aromatic ring-hydroxylating oxygenases; PIPT, phosphatidylinositol transfer proteins; Bet v 1, the major pollen allergen of white birch, Betula verrucosa; CoxG, carbon monoxide dehydrogenase subunit G (gram-negative bacteria); CalC, and related proteins.

Abbreviations

ACAT :

acyl-CoA:cholesterol acyl transferase

ACOT :

acyl-CoA thioesterase

BFIT2 :

brown fat-inducible thioesterase-2

CDCA :

chenodeoxycholic acid

CERT :

ceramide transfer protein

COL4A3BP :

collagen type IV alpha 3 binding protein

DLC :

deleted in liver cancer

FFAT :

peptide EFFDAxE

FHA :

forkhead-associated phosphopeptide binding domain

MENTAL :

MLN64-N terminal domain

MLN64 :

metastatic axillary lymph node 64 kDa protein

NPC :

Niemann –Pick type C disease

PC :

phosphatidylcholine

PCTP :

phosphatidylcholine transfer protein

PH :

pleckstrin homology domain

SAM :

sterile alpha domain

SREBP-2 :

sterol regulatory element binding protein-2

StAR :

steroidogenic acute regulatory protein

START :

StAR-related lipid transfer domain

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Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, University of Louisville, 40292, Louisville, KY, USA

    Barbara J. Clark Ph.D.

  2. Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 79430, Lubbock, TX, USA

    Douglas M. Stocco Ph.D.

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Correspondence to Barbara J. Clark Ph.D. .

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  1. Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA

    Barbara J. Clark

  2. Cell Biology and Biochemistry, Texas Tech Univ. Health Sciences Center, Lubbock, Texas, USA

    Douglas M. Stocco

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Clark, B., Stocco, D. (2014). An Introduction to the Steroidogenic Acute Regulatory Protein (StAR)-Related Lipid Transfer Domain Protein Family. In: Clark, B., Stocco, D. (eds) Cholesterol Transporters of the START Domain Protein Family in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1112-7_1

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