Natively unfolded proteins play key roles in normal and pathological biochemical processes. This category of proteins remains, however, beyond the reach of classical structural biology because of their inherent conformational heterogeneity. When confined in weakly aligning media, natively unfolded proteins such as alpha-synuclein, the major component of abnormal aggregates in the brain of patients with Parkinson's disease, display surprisingly variable NMR dipolar couplings as a function of position along the chain, suggesting the presence of residual secondary or tertiary structure. Here we show that the variation of NMR dipolar couplings and heteronuclear relaxation rates in alpha-synuclein closely follows the variations of the bulkiness of amino acids along the polypeptide chain. Our results demonstrate that the bulkiness of amino acids defines the local conformations and dynamics of alpha-synuclein and other natively unfolded proteins. Deviations from this random coil behavior can provide insight into residual secondary structure and long-range transient interactions in unfolded proteins.