Page 8 - Annual Report 2020

Rhoderick Brown, Ph.D.
Membrane Biochemistry and Molecular Biophysics
SECTION LEADER / PROFESSOR
“Unraveling how sphingolipid transfer proteins control inflammation and programmed cell
death by regulating
the homeostatic levels and locations of sphingolipid in cells
is of fundamental importance for developing new therapeutic approaches to treat diseases such
as cancer.”
Rhoderick “Rick” Brown
Yong-guang Gao Lucy Malinina
Our research focuses on proteins that interact from mammals, plants and fungi enabled X-ray dif-
with membrane lipids. Such proteins include
sphingolipid transfer proteins that shuttle sphingolipids between intracellular membranes to help form and maintain ‘raft’ microdomains present in certain membranous organelles. Other proteins being studied are modular lipid-binding domains (e.g. C2-domains) that act as membrane targeting and anchoring devices for select proteins that must translocate to cell membranes to function. Our clon- ing of glyco(sphingo)lipid transfer proteins (GLTPs)
fraction determination of their molecular structures both in glycolipid-free form and complexed with different glycolipids. GLTP utilizes a novel protein fold, i.e. GLTP-fold, to recognize and bind glycolipids for intermembrane transfer. We also learned how: i) different glycolipids are accommodated within the glycolipid binding site; ii) the function played by tryptophans in glycolipid binding and membrane interaction; iii) the structural basis for more focused glycolipid selectivity by fungal GLTP and the human
SUMMARY
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