6Z3E

Crystal structure of GDP-bound human GIMAP5, amino acid residues 1-276

Summary for 6Z3E

• Entry DOI: 10.2210/pdb6z3e/pdb
• Descriptor: GTPase IMAP family member 5, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: gtpase, immunity, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 31606.73

Authors

Schwefel, D.,Daumke, O. (deposition date: 2020-05-20, release date: 2021-12-01, Last modification date: 2025-07-16)

Primary citation

Park, A.Y.,Leney-Greene, M.,Lynberg, M.,Gabrielski, J.Q.,Xu, X.,Schwarz, B.,Zheng, L.,Balasubramaniyam, A.,Ham, H.,Chao, B.,Zhang, Y.,Matthews, H.F.,Cui, J.,Yao, Y.,Kubo, S.,Chanchu, J.M.,Morawski, A.R.,Cook, S.A.,Jiang, P.,Ravell, J.C.,Cheng, Y.H.,George, A.,Faruqi, A.,Pagalilauan, A.M.,Bergerson, J.R.E.,Ganesan, S.,Chauvin, S.D.,Aluri, J.,Edwards-Hicks, J.,Bohrnsen, E.,Tippett, C.,Omar, H.,Xu, L.,Butcher, G.W.,Pascall, J.,Karakoc-Aydiner, E.,Kiykim, A.,Maecker, H.,Tezcan, I.,Esenboga, S.,Heredia, R.J.,Akata, D.,Tekin, S.,Kara, A.,Kuloglu, Z.,Unal, E.,Kendirli, T.,Dogu, F.,Karabiber, E.,Atkinson, T.P.,Cochet, C.,Filhol, O.,Bosio, C.M.,Davis, M.M.,Lifton, R.P.,Pearce, E.L.,Daumke, O.,Aytekin, C.,Sahin, G.E.,Aksu, A.U.,Uzel, G.,Koneti Rao, V.,Sari, S.,Dalgic, B.,Boztug, K.,Cagdas, D.,Haskologlu, S.,Ikinciogullari, A.,Schwefel, D.,Vilarinho, S.,Baris, S.,Ozen, A.,Su, H.C.,Lenardo, M.J.
GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.
Nat.Immunol., 25:282-293, 2024

PubMed Abstract: Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals.

PubMed: 38172257
DOI: 10.1038/s41590-023-01691-y

Experimental method

X-RAY DIFFRACTION (2.80038678769 Å)