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. Author manuscript; available in PMC: 2012 Jun 1.
Published in final edited form as: Curr Opin Genet Dev. 2011 Feb 1;21(3):286–294. doi: 10.1016/j.gde.2011.01.003

Figure 2. Three-dimensional mapping of disease-causing amino acid substitutions in TUBB2B, TUBB3, and TUBA1A.

Figure 2

Functional domains of tubulin are colored as per Figure 1A–E, and residues altered by mutations are highlighted in red. Row 1: Panel depicting mutations altering residues located in the GTP binding pocket, and regions of heterodimer stability, and longitudinal and lateral interactions. “Side views” are shown for each tubulin, and an additional “longitudinal” view is shown for TUBA1A. Row 2: Panel depicting mutations altering residues located in regions of MAP/motor protein interactions. “Topdown” view onto the external helices of tubulin is shown. (A, TUBB2B: PMG) Substitutions in TUBB2B that cause polymicrogyria alter amino acids in domains important for GTP binding, heterodimer stability, and longitudinal interactions (row 1), but are not located in regions that mediate lateral interactions (row 1) or MAP/Motor protein binding (row 2). (A, TUBB3: MCD) Substitutions in TUBB3 that cause gyral malformations are located primarily in rgions that regulate GTP binding, heterodimer stability, and longitudinal and lateral interactions (row 1). Exceptions are M388 and A302 (row 2). A302 is located within a loop that could be important for both heterodimer stability and MAP/motor protein interactions. Similarly, M388 could also regulate MAP/motor protein interactions, and is in proximity to residues at the plus-end of β-tubulin that mediate inter-heterodimer contacts. (A, TUBB3: CFEOM3) Substitutions in TUBB3 that cause axon guidance defects and CFEOM3 are largely found in regions of MAP/motor protein interactions (row 2). The exceptions are R62 and A302, the former of which is located in a loop mediating lateral interactions. (B, TUBA1A: LIS to MCD) Substitutions in TUBA1A are located in all major functional domains. PMG = polymicrogyria, MCD = malformations of cortical development, CFEOM3 = congenital fibrosis of the extraocular muscles type 3, LIS = lissencephaly.