8SH7

TUBB4B and TUBA1A Heterodimer from Human Respiratory Doublet Microtubules

Summary for 8SH7

• Entry DOI: 10.2210/pdb8sh7/pdb
• EMDB information: 40480
• Descriptor: Tubulin alpha-1A chain, Tubulin beta-4B chain, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: cilia, axoneme, microtubule, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 101056.95

Authors

Anderson, J.R.,Gui, M.,Brown, A. (deposition date: 2023-04-13, release date: 2024-05-01, Last modification date: 2024-11-20)

Primary citation

Dodd, D.O.,Mechaussier, S.,Yeyati, P.L.,McPhie, F.,Anderson, J.R.,Khoo, C.J.,Shoemark, A.,Gupta, D.K.,Attard, T.,Zariwala, M.A.,Legendre, M.,Bracht, D.,Wallmeier, J.,Gui, M.,Fassad, M.R.,Parry, D.A.,Tennant, P.A.,Meynert, A.,Wheway, G.,Fares-Taie, L.,Black, H.A.,Mitri-Frangieh, R.,Faucon, C.,Kaplan, J.,Patel, M.,McKie, L.,Megaw, R.,Gatsogiannis, C.,Mohamed, M.A.,Aitken, S.,Gautier, P.,Reinholt, F.R.,Hirst, R.A.,O'Callaghan, C.,Heimdal, K.,Bottier, M.,Escudier, E.,Crowley, S.,Descartes, M.,Jabs, E.W.,Kenia, P.,Amiel, J.,Bacci, G.M.,Calogero, C.,Palazzo, V.,Tiberi, L.,Blumlein, U.,Rogers, A.,Wambach, J.A.,Wegner, D.J.,Fulton, A.B.,Kenna, M.,Rosenfeld, M.,Holm, I.A.,Quigley, A.,Hall, E.A.,Murphy, L.C.,Cassidy, D.M.,von Kriegsheim, A.,Papon, J.F.,Pasquier, L.,Murris, M.S.,Chalmers, J.D.,Hogg, C.,Macleod, K.A.,Urquhart, D.S.,Unger, S.,Aitman, T.J.,Amselem, S.,Leigh, M.W.,Knowles, M.R.,Omran, H.,Mitchison, H.M.,Brown, A.,Marsh, J.A.,Welburn, J.P.I.,Ti, S.C.,Horani, A.,Rozet, J.M.,Perrault, I.,Mill, P.
Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules.
Science, 384:eadf5489-eadf5489, 2024

PubMed Abstract: Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the isotype that specifically perturbed centriole and cilium biogenesis. Distinct variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.

PubMed: 38662826
DOI: 10.1126/science.adf5489

Experimental method

ELECTRON MICROSCOPY (2.8 Å)