Details

Autor(en) / Beteiligte

• Chen, Liqing
• DiGiammarino, Enrico
• Zhou, Xiaoyin E.
• Wang, Yujun
• Toh, Diana
• Hodge, Thomas W.
• Meehan, Edward J.

Titel

High Resolution Crystal Structure of Human Rab9 GTPase

Ist Teil von

• The Journal of biological chemistry, 2004-09, Vol.279 (38), p.40204-40208

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2004

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• Rab GTPases and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. Rab9 mediates late endosome to trans-Golgi transport and has recently been found to be a key cellular component for human immunodeficiency virus-1, Ebola, Marburg, and measles virus replication, suggesting that it may be a novel target in the development of broad spectrum antiviral drugs. As part of our structure-based drug design program, we have determined the crystal structure of a C-terminally truncated human Rab9 (residues 1-177) to 1.25-Å resolution. The overall structure shows a characteristic nucleotide binding fold consisting of a six-stranded β-sheet surrounded by five α-helices with a tightly bound GDP molecule in the active site. Structure-based sequence alignment of Rab9 with other Rab proteins reveals that its active site consists of residues highly conserved in the Rab GTPase family, implying a common catalytic mechanism. However, Rab9 contains seven regions that are significantly different in conformation from other Rab proteins. Some of those regions coincide with putative effector-binding sites and switch I and switch II regions identified by structure/sequence alignments. The Rab9 structure at near atomic resolution provides an excellent model for structure-based antiviral drug design.