The proteins SMN and Gemin2 form the conserved core of the larger eponymous SMN complex, which also contains Gemins3-8 and unrip in an unknown stoichiometry. The complex facilitates the ordered assembly of seven Sm proteins onto a conserved site of an snRNA to form spliceosomal snRNP cores. A deficit in functional SMN as a consequence of deletions or loss-of-function mutations in the gene SMN1 underlies the disease spinal muscular atrophy (SMA), a severe neurodegenerative disorder and leading genetic cause of infant mortality. Here, the NMR solution structure of the interacting domains of human SMN and Gemin2 is reported. The Gemin2-SMN heterodimer forms a novel all α-helical fold, comprising a single SMN helix embedded in an elongated, hydrophobic cavity of Gemin2. The interface between SMN and Gemin2 is mediated through highly conserved residues on the hydrophobic face of the amphipathic SMN helix and on four Gemin2 helices far separated in primary sequence. Mutations of interfacial residues predicted by the structure to be essential, but not of known disease mutations, disrupted the SMN-Gemin2 interaction. A number of biophysical studies also showed that unbound Gemin2 undergoes a significant conformational change upon SMN binding to become more compact, but belied reports of a Gemin2 self-interaction. A related set of investigations conducted on the full-length orthologous S. pombe Gemin2-SMN proteins showed that the complex occupies small, discrete oligomers that self-associate to form larger assemblies; its apparently large molecular weight by analytical size-exclusion chromatography results from an elongated, partially unstructured state. Together, these NMR and biophysical studies of SMN and Gemin2 provide the first high-resolution glimpse of the SMN-Gemin2 heterodimer, establish a framework for future structure-function studies investigating snRNP biogenesis and SMA pathogenesis and provide new valuable insight into the overall oligomerization state of the SMN complex.