The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms a cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the "glutamic finger," conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.

Problem Racial and ethnic disparities in health outcomes remain pervasive in the U.S. health care system. Increasing the diversity of the physician workforce is recognized as an important component of addressing these disparities. Holistic review, which gives balanced consideration to applicants’ academic metrics, experiences, and attributes, has gained popularity in undergraduate medical education and led to improvement in student diversity. Limited research has investigated how holistic review and other strategies can be implemented in graduate medical education to enhance diversity. Approach The internal medicine (IM) residency program of the John P. and Kathrine G. McGovern Medical School implemented a pilot intervention in academic years (AY) 2016–2017 and 2017–2018 aimed at increasing the number of matriculating residents who are underrepresented in medicine (URM). The intervention included (1) using holistic review in the process of selecting applicants for interview, (2) standardizing the interview encounters, and (3) explicitly highlighting the program’s commitment to diversity on interview days. Outcomes From AY 2015–2016 (preintervention) to AY 2017–2018, the percentage of URM applications reviewed increased from 14.1% (180/1,276) to 20.4% (183/897), the proportion of URM applicants interviewed rose from 16.0% (60/374) to 24.5% (95/388), and the proportion of URM residents matriculating increased from 12.5% (5/40) to 31.7% (13/41). Next Steps Further efforts are needed to expand the pool of URM applicants at McGovern and elsewhere and to identify how holistic review can be widely employed in other IM residency programs and in other specialties.