4UEX

Structure of human Saposin A at lysosomal pH

4UEX の概要

• エントリーDOI: 10.2210/pdb4uex/pdb
• 分子名称: PROSAPOSIN (2 entities in total)
• 機能のキーワード: lipid binding protein, saposin a, saposin, sap, lipid transfer protein, sphingolipid activator protein
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18605.56

構造登録者

Hill, C.H.,Read, R.J.,Deane, J.E. (登録日: 2014-12-20, 公開日: 2015-07-15, 最終更新日: 2024-11-13)

主引用文献

Hill, C.H.,Read, R.J.,Deane, J.E.
Structure of Human Saposin a at Lysosomal Ph.
Acta Crystallogr.,Sect.D, 71:895-, 2015

PubMed Abstract: The saposins are essential cofactors for the normal lysosomal degradation of complex glycosphingolipids by acid hydrolase enzymes; defects in either saposin or hydrolase function lead to severe metabolic diseases. Saposin A (SapA) activates the enzyme β-galactocerebrosidase (GALC), which catalyzes the breakdown of β-D-galactocerebroside, the principal lipid component of myelin. SapA is known to bind lipids and detergents in a pH-dependent manner; this is accompanied by a striking transition from a `closed' to an `open' conformation. However, previous structures were determined at non-lysosomal pH. This work describes a 1.8 Å resolution X-ray crystal structure determined at the physiologically relevant lysosomal pH 4.8. In the absence of lipid or detergent at pH 4.8, SapA is observeed to adopt a conformation closely resembling the previously determined `closed' conformation, showing that pH alone is not sufficient for the transition to the `open' conformation. Structural alignments reveal small conformational changes, highlighting regions of flexibility.

PubMed: 26144235
DOI: 10.1107/S2053230X15008584

実験手法

X-RAY DIFFRACTION (1.8 Å)